Heterocyclic quinones as pharmaceutical agents

ABSTRACT

Pyrrolylquinones and indolylquinones useful for treating diseases such as neurodegenerative disease, viral infections and proliferative disease are described, along with methods of making such compounds and pharmaceutical formulations containing such compounds.

FIELD OF THE INVENTION

[0001] This invention relates to synthetic methods for the preparationof pyrrolylquinones and indolylquinones, the compounds so prepared, anduses thereof in the treatment of disease.

BACKGROUND OF THE INVENTION

[0002] Demethylasterriquinone is a natural product that was discoveredby Merck to have the ability to activate the insulin receptor, andthereby to act orally in glucose lowering in mouse models of diabetes.They have also shown that this compound can activate the TrkA nervegrowth factor (neutrophin) receptor. They have further developed asynthetic version identified as “Compound 2” below. See generally Zhanget al., Science 284, 974-977 (1999); Liu et al., J. Med. Chem. 43,3487-3494 (2000).

[0003] U.S. Pat. No. 5,786,488 to Tang et al. proposes synthesis ofmono- and bis-indolylquinones using alkali conditions and metalcarbonates.

[0004] Harris, et al., A One-Pot, Two-Step Synthesis of TetrahydroAsterriquinone E, Organic Letters 1999, 1(3):431-433 discusses aprocedure similar to the '488 patent to produce asterriquinone E.

[0005] U.S. Pat. No. 5,780,496 to Tang et al. proposes the utility ofindolylquinones as agents for treatment of protein tyrosine kinase cellproliferative disorders.

[0006] U.S. Pat. No. 6,011,058 to Zalkow et al. proposes targeting Cdc25with seco-cholestane derivatives.

[0007] Ono et al., Inhibition of HIV-Reverse Transcriptase Activity byAsterriquinone and its Analogues, Biochem. Biophys. Res. Commun. 1991,174(1):56-62, discusses the ability of asterriquinone and asterriquinonederivatives B1-4, C1-1 and D-1 to inhibit HIV-reverse transcriptase.

[0008] U.S. Pat. No. 6,376,529 to Tang et al. proposes the use ofmonoindolylquinones and bisindolylquinones to treat PTK-related cellproliferative disorders and diabetes mellitus.

SUMMARY OF THE INVENTION

[0009] A first aspect of the present invention is an acid-catalyzedmethod of producing a compound of Formula I:

[0010] wherein:

[0011] R₁ and R₃ are each independently hydrogen, OH, SH, halo, amino,alkoxy, aminoalkyl, alkyl, aryl, acyloxy, or (acyloxy)alkyl

[0012] R₂ is hydrogen, aryl, heteroaryl, indolyl, alkyl, alkoxy,phenoxy, anilino, amino, halo, acyloxy, or (acyloxy)alkyl;

[0013] or R₁ and R₂ together form an aromatic ring (e.g., R1 and R2together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—);

[0014] R₅ is hydrogen, C₁-C₇ alkyl, C₂-C₇ alkenyl, C₂-C₇ alkynyl,arylalkyl, or aryl;

[0015] R₄ is hydrogen, branched or unbranched saturated C₁-C_(n) alkyl,branched or unbranched unsaturated C₁-C_(n) alkyl, alkylcarboxy,C₂-C_(m) alkenyl, alkynyl, alkenylcarboxy, aryl, alkylaryl hydroxy,hydroxyalkyl, C₁-C_(n) alkoxy, nitro, halo, trihalomethyl, amido,carboxamido, carboxy, sulfonyl, sulfonamido, amino, mercapto, or2-methylbut-2-en-4-yl, wherein n is an integer from 2-12, preferably2-7, and m is an integer from 3-12, preferably 3-7; and

[0016] R₆ and R₇ are each independently hydrogen, cycloalkyl, alkyl,alkoxy, halo, aryl, heteroaryl, phenoxy, anilino, amino, or form part ofan aromatic ring ((e.g., R6 and R7 together form —CH═CH—CH—,—CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—) wherein said aromatic ring may beunsubstituted or substituted 1, 2 or 3 times with cycloalkyl, alkyl,alkoxy, halo, aryl, heteroaryl, phenoxy, anilino, amino;

[0017] which method comprises:

[0018] reacting a substituted or unsubstituted2,5-dichloro-1,4-benzoquinone compound of the formula:

[0019]  wherein R₁, R₂ and R₃ are as defined above;

[0020] with at least one pyrrole of the formula:

[0021]  wherein R₄—R₇ are as defined above,

[0022] in a polar organic solvent and in the presence of an acid toproduce a first intermediate; and then

[0023] reacting the first intermediate with an oxidization agent toproduce said compound of formula I. In some embodiments of theforegoing, n is 2-7 and m is 3-7. In some embodiments, the methodfurther comprises: reacting said compound of formula I with an alkalimetal hydroxide to produce a compound of the formula:

[0024]  wherein R₂ and R₄—R₇ are as defined above. The organic solventmay be, for example, an aprotic solvent selected from the groupconsisting of tetrahydrofuran (THF), acetonitrile, and mixtures thereof.In some embodiments, the acid may be HCl, H₂SO₄, AcOH (acetic acid), ormixtures thereof. In some embodiments the oidization agent isdichlorodicyanobenzoquinone, Ag₂CO₃, or mixtures thereof. The reactionmay be conducted at any suitable temperature, such as from about −10° C.to about 100° C.

[0025] A second aspect of the present invention is an acid-catalyzedmethod of producing a compound of formula V:

[0026] wherein:

[0027] R₁ and R₃ are each independently OH, SH, halo, amino, alkoxy,aminoalkyl, hydrogen, alkyl, aryl, acyloxy, or (acyloxy)alkyl;

[0028] R₂ is hydrogen, aryl, heteroaryl, indolyl, alkyl, alkoxy,phenoxy, anilino, amino, halo, acyloxy, or (acyloxy)alkyl; or

[0029] R₁ and R₂ can constitute part of an aromatic ring (e.g., R1 andR2 together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—);

[0030] R₅ is hydrogen, C₁-C₇ alkyl, C₂-C₇ alkenyl, C₂-C₇ alkynyl,arylalkyl, or aryl; and

[0031] R₄ and R₆—R₉ are each independently hydrogen, branched orunbranched C₁-C_(n) alkyl, alkylcarboxy, C₂-C_(m) alkenyl, alkynyl,alkenylcarboxy, aryl, alkylaryl, hydroxy, hydroxyalkyl, C₁-C_(n) alkoxy,nitro, halo, trihalomethyl, amido, carboxamido, carboxy, sulfonyl,sulfonamido, amino, mercapto, or 2-methylbut-2-en-4-yl, wherein n is aninteger from 2-12, and m is an integer from 3-12;

[0032] which method comprises:

[0033] reacting a substituted or unsubstituted2,5-dichloro-1,4-benzoquinone compound of the formula:

[0034]  wherein R₁, R₂ and R₃ are as defined above;

[0035] with at least one indole of the formula:

[0036]  wherein R₄—R₉ are as defined above;

[0037] in a polar organic solvent and in the presence of an acid toproduce a first intermediate; and then

[0038] reacting the first intermediate with an oxidization agent toproduce said compound of formula V. In some embodiments, n is 2-7 and mis 3-7. The method may further comprise reacting said compound offormula I with an alkali metal hydroxide to produce a compound of theformula:

[0039]  wherein R₂ and R₄—R₉ are as defined above. In some embodiments,the organic solvent is an aprotic solvent selected from the groupconsisting of tetrahydrofuran (THF), acetonitrile, and mixtures thereof.The acid may, for example, be HCl, H₂SO₄, AcOH, or mixtures thereof. Theoxidization agent may be dichlorodicyanobenzoquinone, Ag₂CO₃ orcombinations thereof. The reaction may in some embodiments be conductedat a temperature from about −10° C. to about 100° C.

[0040] A further aspect of the present invention is a compound of theformula I:

[0041] wherein:

[0042] R₁ and R₃ are each independently hydrogen, OH, SH, halo, amino,alkoxy, aminoalkyl, alkyl, aryl, acyloxy, or (acyloxy)alkyl;

[0043] R₂ is hydrogen, aryl, heteroaryl, indolyl, alkyl, alkoxy,phenoxy, anilino, amino, halo, acyloxy, or (acyloxy)alkyl;

[0044] or R₁ and R₂ together form an aromatic ring (e.g., R1 and R2together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—);

[0045] R₅ is hydrogen, C₁-C₇ alkyl, C₂-C₇ alkenyl, C₂-C₇ alkynyl,arylalkyl, or aryl;

[0046] R₄ is hydrogen, branched or unbranched saturated C₁-C_(n) alkyl,branched or unbranched unsaturated C₁-C_(n) alkyl, alkylcarboxy,C₂-C_(m) alkenyl, alkynyl, alkenylcarboxy, aryl, alkylaryl hydroxy,hydroxyalkyl, C₁-C_(n) alkoxy, nitro, halo, trihalomethyl, amido,carboxamido, carboxy, sulfonyl, sulfonamido, amino, mercapto, or2-methylbut-2-en-4-yl, wherein n is an integer from 2-7 or 12, and m isan integer from 3-7 or 12; and

[0047] R₆ and R₇ are each independently hydrogen, cycloalkyl, alkyl,alkoxy, halo, aryl, heteroaryl, phenoxy, anilino, amino, or form part ofan aromatic ring (e.g., R6 and R7 together form —CH═CH—CH—,—CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—) wherein said aromatic ring isunsubstituted or substituted 1, 2 or 3 times with cycloalkyl, alkyl,alkoxy, halo, aryl, heteroaryl, phenoxy, anilino, or amino.

[0048] A further aspect of the present invention is a compound of theformula V:

[0049] wherein:

[0050] R₁ and R₃ are each independently OH, SH, halo, amino, alkoxy,aminoalkyl, hydrogen, alkyl, aryl, acyloxy, or (acyloxy)alkyl;

[0051] R₂ is hydrogen, aryl, heteroaryl, indolyl, alkyl, alkoxy,phenoxy, anilino, amino, halo, acyloxy, or (acyloxy)alkyl;

[0052] R₁ and R₂ can constitute part of an aromatic ring (e.g., R1 andR2 together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—).

[0053] R₅ is hydrogen, C₁-C₇ alkyl, C₂-C₇ alkenyl, C₂-C₇ alkynyl,arylalkyl, or aryl; and

[0054] R₄ and R₆—R₉ are each independently hydrogen, branched orunbranched C₁-C_(n) alkyl, alkylcarboxy, C₂-C_(m) alkenyl, alkynyl,alkenylcarboxy, aryl, alkylaryl, hydroxy, hydroxyalkyl, C₁-C_(n) alkoxy,nitro, halo, trihalomethyl, amido, carboxamido, carboxy, sulfonyl,sulfonamido, amino, mercapto, or 2-methylbut-2-en-4-yl, wherein n is aninteger from 2 to 7 or 12, and m is an integer from 3 to 7 or 12.

[0055] A further aspect of the present invention is a method of treatinga proliferative disease in a subject in need thereof, comprisingadministering to said subject, in an amount effective to treat saidproliferative disease, a compound of formula I or V as given above.Examples of such said proliferative diseases include but are not limitedto ovarian cancer, breast cancer, colon cancer, gastric carcinomas,non-small cell lung cancer, and non-Hodgkin's lymphoma.

[0056] A still further aspect of the present invention is a method fortreating a viral infection in a subject so afflicted, said methodcomprising administering to the subject a compound of the formula I or Vas given above in an amount effective to treat the viral disease.Examples of infections which may be treated include Poxviridae,Filoviridae, Herpesviridae, Hepadnaviridae, and Retroviridae infections.

[0057] A still further aspect of the present invention is a method fortreating a neurodegenerative disease in a subject so afflicted, saidmethod comprising administering to the subject a compound of the formulaI or V as given above in an amount effective to treat saidneurodegenerative disease. Examples of neurodegenerative diseases whichmay be so treated include but are not limited to Alzheimer's disease,Parkinson's disease, multiple sclerosis, and amyotropic lateralsclerosis.

[0058] A still further aspect of the present invention is the use of acompound of Formula I or Formula V (an active agent) as described abovefor the preparation of a medicament for the treatment of a disorder asdescribed above.

[0059] The present invention is explained in greater detail in thespecification set forth below.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0060] The term “treat” as used herein refers to any type of treatmentthat imparts a benefit to a patient afflicted with a disease, includingimprovement in the condition of the patient (e.g., in one or moresymptoms), delay in the progression of the disease, etc.

[0061] The term “aryl” refers to an aromatic group or substituent whosemolecules have the ring structure characteristic of benzene,naphthalene, phenanthrene, anthracene, etc. (i.e., either the 6-carbonring of benzene or the condensed 6-carbon rings of the other aromaticderivatives). For example, an aryl group may be phenyl (C₆H₅), naphthyl(C₁₀H₇), etc. Aryl groups may be unsubstituted or substituted one, two,three or more times with additional substituents as described below(e.g., alkyl, halo, alkoxy, etc.).

[0062] “Heteroaryl” means an unsubstituted or substituted 5- or6-membered monocyclic hetereoaromatic ring or a 9- or 10-memberedbicyclic hetereoaromatic ring containing 1, 2, 3 or 4 hetereoatoms whichare independently N, S or O. Examples of hetereoaryl rings are furan,thiophene, pyrrole, pyridine, benzimidazole, indole, imidazole,isoquinoline, quinzoline and the like, the corresponding functionalgroups of which are al examples of heteroaryl groups that may be used inthe present invention. Substituents on heteroaryl groups include thoseother as defined herein are included in the definition of heteroaryl.

[0063] “Alkyl” as used herein refers to a paraffinic hydrocarbon groupwhich may be derived from an alkane by dropping one hydrogen from theformula. Examples are methyl, ethyl, propyl, isopropyl, butyl,tert-butyl, etc. Unless otherwise specified herein, “alkyl” as usedherein is preferably a loweralkyl, e.g., C1-C4 loweralkyl. “Alkyl”groups as used herein may be saturated or unsaturated, although theunsaturated alkyls may be identified as “alkenyl” or “alkynyl” groups asdescribed below.

[0064] “Cycloalkyl” as used herein means an unsubstituted or substituted3- to 7-membered carbacyclic ring, which may be unsubstituted orsubstituted (e.g., from 3 to 7 times) with substituents as describedherein.

[0065] “Alkenyl” as used herein refers to an alkyl group as definedabove modified to contain at least one double bond (e.g., at least onedegree of unsaturation). Unless otherwise specified herein, “alkenyl” asused herein is preferably a loweralkenyl, e.g., C1-C4 loweralkenyl.

[0066] “Alkynyl” as used herein refers to an alkyl group as definedabove modified to contain at least one triple bond. Unless otherwisespecified herein, “alkynyl” as used herein is preferably a loweralkynyl,e.g., C1-C4 loweralkynyl.

[0067] “Alkoxy” as used herein means a substituent of the formula —OR,where R is alkyl as defined above.

[0068] “Halo” as used herein refers to one of the electronegativeelements of group VIIA of the periodic table (e.g., fluoro, chlorobromo, iodo).

[0069] “Amino” refers to the —NH₂ group.

[0070] “Aminoalkyl” refers to a group of the formula —NRR′, where atleast one, or both, of R and R′ are alkyl as defined above. One of R andR′ may optionally be H.

[0071] “Acyl” refers to an organic acid group in which the OH of thecarboxyl group is removed so that a bond may be formed. Thus an acylgroup may be generally represented by the formula RCO—, where R is asubstituent as described herein (e.g., alkyl, aryl, arylalkyl), O isdouble bonded to the carbon, and the bond drawn in the structure is tothe carbon shown in the structure). Examples include, but are notlimited to acetyl, benzoyl, etc.

[0072] “Acyloxy” as used herein refers to a group of the formula —OR′,where R′ is acyl as defined above.

[0073] “(Acyloxy)alkyl” as used herein refers to a group of the formula—R—OR′, where R′ is acyl as defined above and R is alkyl as definedabove.

[0074] “Arylalkyl” as used herein refers to a group of the formula —RR″,where R″ is aryl as defined above and R is alkyl as defined above. Anexample is benzyl.

[0075] The term “pharmaceutically acceptable” as used herein means thatthe compound or composition is suitable for administration to a subjectto achieve the treatments described herein, without unduly deleteriousside effects in light of the severity of the disease and necessity ofthe treatment.

[0076] The present invention is primarily concerned with the treatmentof human subjects, but the invention may also be carried out on animalsubjects, particularly mammalian subjects such as mice, rats, dogs,cats, livestock and horses for veterinary purposes, and for drugscreening and drug development purposes.

[0077] 1. Active Compounds

[0078] The methods of the present invention include the administrationof compounds of Formula I, while pharmaceutical compositions of thepresent invention comprise compounds of Formula I as described above.

[0079] Compounds illustrative of the compounds of Formula (I) aboveinclude:

[0080]2-tert-Butyl-3,6-dihydroxy-5-(5-phenethyl-4-phenyl-1H-pyrrol-3-yl)-[1,4]benzoquinone;

[0081] Acetic acid4-acetoxymethoxy-2-(5-benzyloxymethyl-4-methyl-1H-pyrrol-3-yl)-3,6-dioxo-5-phenyl-cyclohexa-1,4-dienyloxymethylester; and

[0082] Acetic acid4-acetoxy-2-(2-cyclopropyl-4,5,6,7-tetrahydro-1H-indol-3-yl)-5-methyl-3,6-dioxo-cyclohexa-1,4-dienylester.

[0083] The methods of the present invention include the administrationof compounds of Formula V, while pharmaceutical compositions of thepresent invention comprise compounds of Formula V as given above.Compounds illustrative of the compounds of Formula (V) above include:2,5-Dichloro-3-(1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(2-metthyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(2,5dimethyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(5-methoxy-2-methyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(5-chloro-2-methyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(2-cyclopropyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(2-phenyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(1-methyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(2-ethyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(2-isopropyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(2-tert-butyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-[2-(1-methyl-cyclopropyl)-1H-indol-3-yl]-[1,4]benzoquinone;2,5-Dichloro-3-[2-(1-methyl-cyclohexyl)-1H-indol-3-yl]-[1,4]benzoquinone;3-(4-Fluoro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(4-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(4-Bromo-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;2,5-Dichloro-3-(4-methoxy-1H-indol-3-yl)-[1,4]benzoquinone;3-(4-Benzyloxy-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;2,5-dichloro-3-(4-methyl-1H-indol-3-yl)-[1,4]benzoquinone;3-(5-Fluoro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(5-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(5-Bromo-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;2,5-Dichloro-3-(5-hydroxy-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(5-methoxy-1H-indol-3-yl)-[1,4]benzoquinone;3-(5-Benzyloxy-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;2,5-Dichloro-3-(5-methyl-1H-indol-3-yl)-[1,4]benzoquinone;3-(6-Fluoro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(6-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(6-Bromo-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;2,5-Dichloro-3-(6-methyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(7-propyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(7-methyl-1H-indol-3-yl)-[1,4]benzoquinone;3-(7-tert-butyl-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;2,5-Dichloro-3-(7-phenyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dichloro-3-(7-methoxy-1H-indol-3-yl)-[1,4]benzoquinone;3-(7-Benzyloxy-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(7-Fluoro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(7-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(7-Bromo-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(7-Benzyl-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;2,5-Dichloro-3-[7-(2-methyl-benzyl)-1H-indol-3-yl]-[1,4]benzoquinone;3-(1H-Benzo[g]indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(2,6-Dimethyl-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(2,7-Dimethyl-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(6,7-Dimethyl-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(5,6-Methylenedioxy-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;3-(5,6-Dimethoxy-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;2,5-Dihydroxy-3-(1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(2-metthyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(2,5dimethyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(5-methoxy-2-methyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(5-chloro-2-methyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(2-cyclopropyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(2-phenyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(1-methyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(2-ethyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(2-isopropyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(2-tert-butyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-[2-(1-methyl-cyclopropyl)-1H-indol-3-yl]-[1,4]benzoquinone;2,5-Dihydroxy-3-[2-(1-methyl-cyclohexyl)-1H-indol-3-yl]-[1,4]benzoquinone;3-(4-Fluoro-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(4-Chloro-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(4-Bromo-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;2,5-Dihydroxy-3-(4-methoxy-1H-indol-3-yl)-[1,4]benzoquinone;3-(4-Benzyloxy-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;2,5-dihydroxy-3-(4-methyl-1H-indol-3-yl)-[1,4]benzoquinone;3-(5-Fluoro-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(5-Chloro-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(5-Bromo-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;2,5-Dihydroxy-3-(5-hydroxy-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(5-methoxy-1H-indol-3-yl)-[1,4]benzoquinone;3-(5-Benzyloxy-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;2,5-Dihydroxy-3-(5-methyl-1H-indol-3-yl)-[1,4]benzoquinone;3-(6-Fluoro-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(6-Chloro-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(6-Bromo-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;2,5-Dihydroxy-3-(6-methyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(7-propyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(7-methyl-1H-indol-3-yl)-[1,4]benzoquinone;3-(7-tert-butyl-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone2,5-Dihydroxy-3-(7-phenyl-1H-indol-3-yl)-[1,4]benzoquinone;2,5-Dihydroxy-3-(7-methoxy-1H-indol-3-yl)-[1,4]benzoquinone;3-(7-Benzyloxy-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(7-Fluoro-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(7-Chloro-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(7-Bromo-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(7-Benzyl-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone;2,5-Dihydroxy-3-[7-(2-methyl-benzyl)-1H-indol-3-yl]-[1,4]benzoquinone;3-(1H-Benzo[g]indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(2,6-Dimethyl-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(2,7-Dimethyl-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(6,7-Dimethyl-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;3-(5,6-Methylenedioxy-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone;and 3-(5,6-Dimethoxy-1H-indol-3-yl)-2,5-dihydroxy-[1,4]benzoquinone.

[0084] The active compounds disclosed herein can, as noted above, beprepared in the form of their pharmaceutically acceptable salts.Pharmaceutically acceptable salts are salts that retain the desiredbiological activity of the parent compound and do not impart undesiredtoxicological effects. Examples of such salts are (a) acid additionsalts formed with inorganic acids, for example hydrochloric acid,hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid and thelike; and salts formed with organic acids such as, for example, aceticacid, oxalic acid, tartaric acid, succinic acid, maleic acid, fumaricacid, gluconic acid, citric acid, malic acid, ascorbic acid, benzoicacid, tannic acid, palmitic acid, alginic acid, polyglutamic acid,naphthalenesulfonic acid, methanesulfonic acid, p-toluenesulfonic acid,naphthalenedisulfonic acid, polygalacturonic acid, and the like; (b)salts formed from elemental anions such as chlorine, bromine, andiodine, and (c) salts derived from bases, such as ammonium salts, alkalimetal salts such as those of sodium and potassium, alkaline earth metalsalts such as those of calcium and magnesium, and salts with organicbases such as dicyclohexylamine and N-methyl-D-glucamine.

[0085] 2. Pharmaceutical Formulations

[0086] The active compounds described above may be formulated foradministration in a pharmaceutical carrier in accordance with knowntechniques. See, e.g., Remington, The Science And Practice of Pharmacy(9^(th) Ed. 1995). In the manufacture of a pharmaceutical formulationaccording to the invention, the active compound (including thephysiologically acceptable salts thereof) is typically admixed with,inter alia, an acceptable carrier. The carrier must, of course, beacceptable in the sense of being compatible with any other ingredientsin the formulation and must not be deleterious to the patient. Thecarrier may be a solid or a liquid, or both, and is preferablyformulated with the compound as a unit-dose formulation, for example, atablet, which may contain from 0.01 or 0.5% to 95% or 99% by weight ofthe active compound. One or more active compounds may be incorporated inthe formulations of the invention, which may be prepared by any of thewell known techniques of pharmacy consisting essentially of admixing thecomponents, optionally including one or more accessory ingredients.

[0087] The formulations of the invention include those suitable fororal, rectal, topical, buccal (e.g., sub-lingual), vaginal, parenteral(e.g., subcutaneous, intramuscular, intradermal, or intravenous),topical (i.e., both skin and mucosal surfaces, including airwaysurfaces) and transdermal administration, although the most suitableroute in any given case will depend on the nature and severity of thecondition being treated and on the nature of the particular activecompound which is being used.

[0088] Preferred routes of parenteral administration include intrathecalinjection, including directly into the tumor, and intraventricularinjection into a ventricle of the brain.

[0089] Formulations suitable for oral administration may be presented indiscrete units, such as capsules, cachets, lozenges, or tablets, eachcontaining a predetermined amount of the active compound; as a powder orgranules; as a solution or a suspension in an aqueous or non-aqueousliquid; or as an oil-in-water or water-in-oil emulsion. Suchformulations may be prepared by any suitable method of pharmacy whichincludes the step of bringing into association the active compound and asuitable carrier (which may contain one or more accessory ingredients asnoted above). In general, the formulations of the invention are preparedby uniformly and intimately admixing the active compound with a liquidor finely divided solid carrier, or both, and then, if necessary,shaping the resulting mixture. For example, a tablet may be prepared bycompressing or molding a powder or granules containing the activecompound, optionally with one or more accessory ingredients. Compressedtablets may be prepared by compressing, in a suitable machine, thecompound in a free-flowing form, such as a powder or granules optionallymixed with a binder, lubricant, inert diluent, and/or surfaceactive/dispersing agent(s). Molded tablets may be made by molding, in asuitable machine, the powdered compound moistened with an inert liquidbinder.

[0090] Formulations suitable for buccal (sub-lingual) administrationinclude lozenges comprising the active compound in a flavoured base,usually sucrose and acacia or tragacanth; and pastilles comprising thecompound in an inert base such as gelatin and glycerin or sucrose andacacia.

[0091] Formulations of the present invention suitable for parenteraladministration comprise sterile aqueous and non-aqueous injectionsolutions of the active compound, which preparations are preferablyisotonic with the blood of the intended recipient. These preparationsmay contain anti-oxidants, buffers, bacteriostats and solutes whichrender the formulation isotonic with the blood of the intendedrecipient. Aqueous and non-aqueous sterile suspensions may includesuspending agents and thickening agents. The formulations may bepresented in unit\dose or multi-dose containers, for example sealedampoules and vials, and may be stored in a freeze-dried (lyophilized)condition requiring only the addition of the sterile liquid carrier, forexample, saline or water-for-injection immediately prior to use.Extemporaneous injection solutions and suspensions may be prepared fromsterile powders, granules and tablets of the kind previously described.For example, in one aspect of the present invention, there is providedan injectable, stable, sterile composition comprising a compound ofFormula (I), or a salt thereof, in a unit dosage form in a sealedcontainer. The compound or salt is provided in the form of alyophilizate which is capable of being reconstituted with a suitablepharmaceutically acceptable carrier to form a liquid compositionsuitable for injection thereof into a subject. The unit dosage formtypically comprises from about 10 mg to about 10 grams of the compoundor salt. When the compound or salt is substantially water-insoluble, asufficient amount of emulsifying agent which is physiologicallyacceptable may be employed in sufficient quantity to emulsify thecompound or salt in an aqueous carrier. One such useful emulsifyingagent is phosphatidyl choline.

[0092] Formulations suitable for rectal administration are preferablypresented as unit dose suppositories. These may be prepared by admixingthe active compound with one or more conventional solid carriers, forexample, cocoa butter, and then shaping the resulting mixture.

[0093] Formulations suitable for topical application to the skinpreferably take the form of an ointment, cream, lotion, paste, gel,spray, aerosol, or oil. Carriers which may be used include petroleumjelly, lanoline, polyethylene glycols, alcohols, transdermal enhancers,and combinations of two or more thereof.

[0094] Formulations suitable for transdermal administration may bepresented as discrete patches adapted to remain in intimate contact withthe epidermis of the recipient for a prolonged period of time.Formulations suitable for transdermal administration may also bedelivered by iontophoresis (see, for example, Pharmaceutical Research 3(6):318 (1986)) and typically take the form of an optionally bufferedaqueous solution of the active compound. Suitable formulations comprisecitrate or bis\tris buffer (pH 6) or ethanol/water and contain from 0.1to 0.2M active ingredient.

[0095] Further, the present invention provides liposomal formulations ofthe compounds disclosed herein and salts thereof. The technology forforming liposomal suspensions is well known in the art. When thecompound or salt thereof is an aqueous-soluble salt, using conventionalliposome technology, the same may be incorporated into lipid vesicles.In such an instance, due to the water solubility of the compound orsalt, the compound or salt will be substantially entrained within thehydrophilic center or core of the liposomes. The lipid layer employedmay be of any conventional composition and may either containcholesterol or may be cholesterol-free. When the compound or salt ofinterest is water-insoluble, again employing conventional liposomeformation technology, the salt may be substantially entrained within thehydrophobic lipid bilayer which forms the structure of the liposome. Ineither instance, the liposomes which are produced may be reduced insize, as through the use of standard sonication and homogenizationtechniques.

[0096] Of course, the liposomal formulations containing the compoundsdisclosed herein or salts thereof, may be lyophilized to produce alyophilizate which may be reconstituted with a pharmaceuticallyacceptable carrier, such as water, to regenerate a liposomal suspension.

[0097] Other pharmaceutical compositions may be prepared from thewater-insoluble compounds disclosed herein, or salts thereof, such asaqueous base emulsions. In such an instance, the composition willcontain a sufficient amount of pharmaceutically acceptable emulsifyingagent to emulsify the desired amount of the compound or salt thereof.Particularly useful emulsifying agents include phosphatidyl cholines,and lecithin.

[0098] In addition to compounds of formula (I) or (V) or their salts,the pharmaceutical compositions may contain other additives, such aspH-adjusting additives. In particular, useful pH-adjusting agentsinclude acids, such as hydrochloric acid, bases or buffers, such assodium lactate, sodium acetate, sodium phosphate, sodium citrate, sodiumborate, or sodium gluconate. Further, the compositions may containmicrobial preservatives. Useful microbial preservatives includemethylparaben, propylparaben, and benzyl alcohol. The microbialpreservative is typically employed when the formulation is placed in avial designed for multidose use. Of course, as indicated, thepharmaceutical compositions of the present invention may be lyophilizedusing techniques well known in the art.

[0099] 3. Dosage and Routes of Administration

[0100] As noted above, the present invention provides pharmaceuticalformulations comprising the active compounds (including thepharmaceutically acceptable salts thereof), in pharmaceuticallyacceptable carriers for oral, rectal, topical, buccal, parenteral,intramuscular, intradermal, or intravenous, and transdermaladministration.

[0101] Preferred routes of parenteral administration include intrathecalinjection, including directly into the tumor, and intraventricularinjection into a ventricle of the brain.

[0102] The therapeutically effective dosage of any one active agent, theuse of which is in the scope of present invention, will vary somewhatfrom compound to compound, and patient to patient, and will depend uponfactors such as the age and condition of the patient and the route ofdelivery. Such dosages can be determined in accordance with routinepharmacological procedures known to those skilled in the art.

[0103] The therapeutically effective dosage of any specific compound,the use of which is in the scope of present invention, will varysomewhat from compound to compound, and patient to patient, and willdepend upon the condition of the patient and the route of delivery. As ageneral proposition, a dosage from about 0.1 to about 50 mg/kg will havetherapeutic efficacy, with all weights being calculated based upon theweight of the active compound, including the cases where a salt isemployed. Toxicity concerns at the higher level may restrict intravenousdosages to a lower level such as up to about 10 mg/kg, with all weightsbeing calculated based upon the weight of the active base, including thecases where a salt is employed. A dosage from about 10 mg/kg to about 50mg/kg may be employed for oral administration. Typically, a dosage fromabout 0.5 mg/kg to 5 mg/kg may be employed for intramuscular injection.Preferred dosages are 1 μmol/kg to 50 μmol/kg, and more preferably 22μmol/kg and 33 μmol/kg of the compound for intravenous or oraladministration. The duration of the treatment is usually once per dayfor a period of two to three weeks or until the condition is essentiallycontrolled. Lower doses given less frequently can be usedprophylactically to prevent or reduce the incidence of recurrence of theinfection.

[0104] 4. Compounds as Antiviral Agents

[0105] There are comparatively fewer antivirals than there areantibiotics. Since viruses engage in much of their infective activity byhijacking a cell's machinery and essentially directing the cell tomanufacture virus particles, agents with antiviral effect mayadditionally inhibit cellular functions in non-infected cells. Forexample, iododeoxyuridine, one of the first antiviral agents, hassignificant systemic toxicity.

[0106] While advances have lead to more advanced compounds, such asacyclovir and AZT, the number of viruses that are currently targeted byantiviral medicine lags far behind that of antibiotics.

[0107] The present invention shows use in several families of viruses,both in traditional antiviral targets and in families that are currentlyunmet with antiviral medication.

[0108] In one embodiment of the invention, compounds of the inventionare effective in treating infection by viruses of the family Poxviridae,such as variola (smallpox), vaccinia, goatpox, swinepox. Examples ofsuch compounds include but are not limited to compounds 6C, 6F, 11C, and8H from Table 3 below.

[0109] It is known in the art that asterriquinone may inhibit HIVreplication by interacting with viral Reverse Transcriptase. In anotherembodiment of the invention, compounds of the invention are effective intreating infection by viruses which utilize a Reverse Transcriptasemechanism, namely viruses of the family Retroviridae. Examples of suchcompounds include but are not limited to the compounds listed in Table 3below.

[0110] Filoviridae infections are characterized by a rapidly acute andoften fatal infection in a large percentage of patients. Additionally,Filoviridae, specifically Ebola, are feared biological weapons agents.Compounds embodying this invention may have utility against Filoviridae,such as Ebola and Marburg.

[0111] Hepadnaviridae exhibit control over the RAS pathway byutilization of viral protein X. Compounds embodying this invention mayhave utility against Hepadnaviridae, such as Hepatitis B.

[0112] Herpesviridae depend on a viral thymadine kinase pathway, thetarget of antivirals such as acyclovir. Compounds embodying thisinvention may have utility against Herpesviridae, such as HSV-1.

[0113] The present invention is explained in greater detail in thefollowing non-limiting Examples.

EXAMPLE 1 HCl Preperation of2,5-dichloro-3-(2-methyl-1H-indol-3-yl)-[1,4]benzoquinone (Procedure A)

[0114] To a solution of 2-methylindole (0.500 g, 3.81 mmol) in THF (30mL) was added 2,5-dichloro-1,4-benzoquinone (1.35 g, 7.62 mmol) at roomtemperature. To this mixture was added concentrated HCl (12 N, 0.38 mL,4.57 mmol) dropwise. After the reaction mixture was stirred for 5 hours(5 h-12 h) at room temperature, DDQ (1.73 g, 7.62 mmol) was added. Afterstirring for 3 hours (3 h-12 h) at room temperature, the mixture wasdiluted with EtOAc (100 mL). The organic solution was washed withsaturated NaHCO₃ (3×100 mL) and brine (100 mL), and dried over Na₂SO₄.The residue was concentrated and purified by flash column chromatographyusing 15% EtOAc in hexane as eluent to afford pure2,5-dichloro-3-(2-methyl-1H-indol-3-yl)-[1,4]benzoquinone (1.13 g, 97%)as a blue solid. Melting point 158-159° C. R_(f)=0.35 (3:7,EtOAc/hexane). ¹H NMR (CDCl₃) δ 8.40 (bs, NH), 7.24-7.11 (m, 5H), 2.26(s, 3H). ¹H NMR (d₆-acetone): δ 10.60 (1H, br s), 7.39 (1H, s), 7.36(1H, d, J=7.8 Hz), 7.24 (1H, d, J=7.8 Hz), 7.10 (1H, t, J=7.8 Hz), 7.01(1H, t, J=7.8 Hz). ¹³C NMR (CDCl₃) δ 177.7, 176.6, 144.3, 139.8, 139.3,136.9, 135.1, 133.1, 126.6, 122.0, 120.5, 119.6, 110.8, 104.8, 13.9. IR(KBr): 3388, 3061, 1676, 1566, 1459, 1250, 1032, 749 cm⁻¹. Anal. Calcd.for C₁₅H₉Cl₂NO₂: C, 58.85; H, 2.96; Cl, 23.16; N, 4.58. Found: C, 58.85;H, 2.96; Cl, 23.16; N, 4.58. HRMS (EI) Calcd. For C₁₅H₉Cl₂NO₂ [M⁺]:305.0010. Found: 305.0002.

EXAMPLE 2 H₂SO₄ Preperation of2,5-dichloro-3-(5-methoxy-1H-indol-3-yl)-[1,4]benzoquinone (Procedure B)

[0115] To a solution of 2,5-dichloro-1,4-benzoquinone (0.242 g, 1.37mmol) in THF (3 mL) was added H₂SO₄ (35 μL, 0.68 mmol) at roomtemperature. To this mixture was added 5-methoxyindole (0.100 g, 0.68mmol). After the reaction mixture was stirred for 1 hour at roomtemperature under nitrogen protection, DDQ (0.232 g, 1.02 mmol) wasadded. After stirring for 2 hours, the mixture was diluted with ethylacetate (100 mL). The organic layer was washed with sat. NaHCO₃ (3×20mL) and brine (20 mL), and dried over Na₂SO₄. The solution wasconcentrated and purified by flash column chromatography using 15% EtOAcin hexane as eluent to afford2,5-dichloro-3-(5-methoxy-1H-indole-3-yl)-[1,4]benzoquinone (0.211 g,96%) as blue needles from benzene/hexane. Melting Point 195-196° C. ¹HNMR (CDCl₃): 6.78 (1H, d, J=2.4 Hz), 6.93 (1H, dd, J=2.1, 8.4 Hz), 7.23(1H, s), 7.34 (1H, d, J=9.0 Hz), 7.54 (1H, d, J=3.0 Hz), 8.62 (1H, brs). ¹³C NMR (d₆-acetone): 55.2, 103.8, 106.7, 112.4, 112.8, 126.5,130.9, 131.0, 131.4, 133.4, 139.8, 143.7, 154.8, 177.8, 178.0. IR (KBr):3328, 3043, 2924, 2855, 1675, 1638, 1543, 1484, 1260, 1227 cm⁻¹. Anal.Calcd. for C₁₅H₉Cl₂NO₃: C, 55.93; H, 2.82; N, 4.35. Found: C, 55.72; H,2.99; N, 4.24.

EXAMPLE 3 AcOH Preperation of2,5-dichloro-3-[2-(1-methyl-cyclopropyl)-1H-indol-3-yl]-[1,4]benzoquinone(Procedure C)

[0116] To a solution of 2,5-dichloro-1,4-benzoquinone (0.177 g, 1.00mmol) in AcOH (2 mL) was added 2-(1methyl-cyclopropyl)indole (0.081 g,0.47 mmol). After the reaction mixture was stirred for 2 h at 50° C.under nitrogen protection, Ag₂CO₃ on Celite® (50%, 0.500 g, 0.90 mmol)was added. After stirring for 4 h at room temperature, the solution wasdiluted with ethyl acetate (100 mL). The organic layer was washed withsat. NaHCO₃ (3×20 mL) and brine (20 mL), and dried over Na₂SO₄. Thesolution was concentrated and purified by flash column chromatographyusing 15% EtOAc in hexane as eluent to afford2,5-dichloro-3-[2-(1-methyl-cyclopropyl)-1H-indol-3-yl]-[1,4]benzoquinone(0.148 g, 90%) as blue needles from benzene/hexane. Melting Point170-171° C. ¹H NMR (d₆-acetone): 0.53-0.60 (1H, m), 0.64-0.70 (1H, m),0.70-0.77 (1H, m), 0.92-0.98 (1H, m), 1.48 (3H, s), 7.01 (1H, dt, J=1.2,7.5 Hz), 7.10 (1H, dt, J=1.2, 7.5 Hz), 7.24 (1H, dd, J=0.6, 7.2 Hz),7.37 (1H, d, J=7.8 Hz), 7.39 (1H, s), 10.70 (1H, s). ¹³C NMR(d₆-acetone): 13.3, 14.1, 15.1, 24.5, 103.6, 111.4, 119.7, 119.9, 121.9,126.8, 133.8, 136.0, 140.4, 140.8, 143.9, 144.0, 177.1, 177.9. IR (KBr):3409, 3059, 3004, 2966, 2927, 1662, 1620, 1567, 1435, 1270, 1241, 1028,755 cm⁻¹. Anal. Calcd. for C₁₈H₁₃Cl₂NO₂: C, 62.45; H, 3.78; N, 4.05.Found: C, 62.30; H, 3.77; N, 3.94.

EXAMPLE 4 Hydrolysis of2,5-dichloro-3-[2-(1-methyl-cyclopropyl)-1H-indol-3-yl]-[1,4]benzoquinone(Procedure D)

[0117] To a refluxing solution of2,5-dichloro-3-[2-(1-methyl-cyclopropyl)-1H-indole-3-yl]-[1,4]benzoquinone(0.056 g, 0.16 mmol) in MeOH (6 mL) was added 10% aqueous NaOH (3 mL)dropwise. After refluxing for a half hour, the mixture was poured intocold water (20 mL). H₂SO₄ (10%) was added to acidify the mixture, whichwas extracted with EtOAc (3×10 mL). The organic layer was washed withbrine (10 mL) and dried over Na₂SO₄. The solution was concentrated andpurified by flash column chromatography (oxalic acid-coated silica gel)using 30% EtOAc in hexane as the eluent to afford2,5-dihydroxy-3-[2-(1-methyl-cyclopropyl)-1H-indol-3-yl]-[1,4]benzoquinone(0.044 g, 87%) as dark blue needles from acetone/hexane. Melting Point103° C. (dec). ¹H NMR (d₆-acetone): 0.55-0.62 (2H, m), 0.81-0.87 (2H,m), 1.45 (3H, s), 6.08 (1H, s), 6.93 (1H, dt, J=0.9, 8.1 Hz), 7.04 (1H,dt, J=1.2, 8.1 Hz), 7.22 (1H, d, J=7.8 Hz), 7.31 (1H, dd, J=0.9, 8.1Hz), 9.0-10.1 (2H, br s), 10.34 (1H, br s). ¹³C NMR (d₆-acetone): 13.3,14.8, 24.4, 101.4, 103.6, 110.8, 112.3, 119.0, 119.5, 121.1, 128.4,135.8, 142.2. IR (KBr): 3300, 3077, 2958, 2924, 1640, 1360, 1190, 746cm⁻¹. HRMS (EI): calculated for C₁₈H₁₅NO₄ 309.1001; found 309.0999.

EXAMPLE 5

[0118] The following indoles were reacted according to the aboveprocedures (procedures A-C, Examples 1-3) to achieve the listed yieldsand stated product. TABLE 1 Procedure Procedure Procedure Indole A^(a)B^(b) C^(b) End Product indole 70% 75% 8 2,5-Dichloro-3-(1H-indol-3-yl)-[1,4]benzoquinone 2-methylindole 97% 96% 22,5-Dichloro-3-(2-metthyl-1H-indol-3-yl)- [1,4]benzoquinone2,5-dimethylindole 91% 2,5-Dichloro-3-(2,5dimethyl-1H-indol-3-yl)-[1,4]benzoquinone 2-methyl-5-methoxyindole^(c) 89%2,5-Dichloro-3-(5-methoxy-2-methyl-1H- indol-3-yl)-[1,4]benzoquinone2-methyl-5-chloroindole^(c) 75% 2,5-Dichloro-3-(5-chloro-2-methyl-1H-indol-3-yl)-[1,4]benzoquinone 2-cyclopropylindole 95%2,5-Dichloro-3-(2-cyclopropyl-1H-indol-3- yl)-[1,4]benzoquinone2-phenylindole 89% 2,5-Dichloro-3-(2-phenyl-1H-indol-3-yl)-[1,4]benzoquinone N-methylindole 87%2,5-Dichloro-3-(1-methyl-1H-indol-3-yl)- [1,4]benzoquinone 2-ethylindole95% 2,5-Dichloro-3-(2-ethyl-1H-indol-3-yl)- [1,4]benzoquinone2-isopropylindole 70% 2,5-Dichloro-3-(2-isopropyl-1H-indol-3-yl)-[1,4]benzoquinone 2-tert-butylindole 54% 90% 22,5-Dichloro-3-(2-tert-butyl-1H-indol-3- yl)-[1,4]benzoquinone2-(1-methylcyclopropyl)indole 46% 1 90% 22,5-Dichloro-3-[2-(1-methyl-cyclopropyl)-1H-indol-3-yl]-[1,4]benzoquinone 2-(1-methylcyclohexyl)indole 50% 24 91%10 2,5-Dichloro-3-[2-(1-methyl-cyclohexyl)-1H-indol-3-yl]-[1,4]benzoquinone 4-fluoroindole  0% 120 16% 42 14% 223-(4-Fluoro-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone4-chloroindole  0% 120 54% 92 3-(4-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 4-bromoindole  0% 120 39% 1443-(4-Bromo-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone4-methoxyindole  2% 0.5 66% 3 2,5-Dichloro-3-(4-methoxy-1H-indol-3-yl)-[1,4]benzoquinone 4-benzyloxyindole  1% 0.5 65% 33-(4-Benzyloxy-1H-indol-3-yl)-2,5- dichloro-[1,4]benzoquinone4-methylindole 39% 21 76% 20 2,5-Dichloro-3-(4-methyl-1H-indol-3-yl)-[1,4]benzoquinone 5-fluoroindole 50% 5 74% 63-(5-Fluoro-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone5-chloroindole 56% 0.5 72% 24 3-(5-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 5-bromoindole 57% 0.5 73% 243-(5-Bromo-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone5-hydroxyindole 52% 0.5  6% 0.52,5-Dichloro-3-(5-hydroxy-1H-indol-3-yl)- [1,4]benzoquinone5-methoxyindole 96% 0.5 2,5-Dichloro-3-(5-methoxy-1H-indol-3-yl)-[1,4]benzoquinone 5-benzyloxyindole 92% 0.53-(5-Benzyloxy-1H-indol-3-yl)-2,5- dichloro-[1,4]benzoquinone5-methylindole 82% 6 72% 2 2,5-Dichloro-3-(5-methyl-1H-indol-3-yl)-[1,4]benzoquinone 6-fluoroindole 37% 5 63% 63-(6-Fluoro-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone6-chloroindole 58% 20 55% 6 3-(6-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 6-benzyloxyindole 14% 2 22% 223-(6-Bromo-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone 6-methylindole63% 1 75% 20 2,5-Dichloro-3-(6-methyl-1H-indol-3-yl)- [1,4]benzoquinone7-methylindole 81% 83% 22 2,5-Dichloro-3-(7-propyl-1H-indol-3-yl)-[1,4]benzoquinone 7-propylindole 82% 6 81% 52,5-Dichloro-3-(7-methyl-1H-indol-3-yl)- [1,4]benzoquinone7-tert-butylindole 81% 6 82% 83-(7-tert-butyl-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone7-phenylindole 66% 12 66% 4 2,5-Dichloro-3-(7-phenyl-1H-indol-3-yl)-[1,4]benzoquinone 7-methoxyindole 13% 20 62% 9 50% 682,5-Dichloro-3-(7-methoxy-1H-indol-3-yl)- [1,4]benzoquinone7-benzyloxyindole 71% 5 65% 6 3-(7-Benzyloxy-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 7-fluoroindole 43   483-(7-Fluoro-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone7-chloroindole 17   96 63   72 3-(7-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 7-bromoindole 34   72 41   483-(7-Bromo-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone 7-benzylindole89   1 3-(7-Benzyl-1H-indol-3-yl)-2,5-dichloro- [1,4]benzoquinone7-o-methylbenzylindole 88   1 2,5-Dichloro-3-[7-(2-methyl-benzyl)-1H-indol-3-yl]-[1,4]benzoquinone 1H-Benzo[g]indole 34% 483-(1H-Benzo[g]indol-3-yl)-2,5-dichloro- [1,4]benzoquinone2,6-dimethylindole 89% 6 3-(2,6-Dimethyl-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 2,7-dimethylindole 59% 2 94% 13-(2,7-Dimethyl-1H-indol-3-yl)-2,5- dichloro-[1,4]benzoquinone6,7-dimethylindole 90% 0.16 88% 4 3-(6,7-Dimethyl-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 5,6-methylenedioxyindole 10% 2 10% 23-(5,6-Methylenedioxy-1H-indol-3-yl)-2,5- dichloro-[1,4]benzoquinone5,6-dimethoxyindole  9% 24 33% 0.5 3-(5,6-Dimethoxy-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone

EXAMPLE 6

[0119] The mono-indolquinone starting products listed in Table 2 werereacted according procedure D (Example 4) to achieve the listed yieldsand stated end product. Also included in this example arecharacterizations of the starting and ending compounds. TABLE 2 StartingProduct Yield End Product2,5-Dichloro-3-(1H-indol-3-yl)-[1,4]benzoquinone 59%2,5-Dihydroxy-3-(1H-indol-3-yl)-[1,4]benzoquinone mp 124-125° C.IR(KBr): 3362, 3062, 2922, 1666, 1645, mp 219-220° C. IR(KBr): 3421,3301, 1666, 1293, 1559, 1248cm⁻¹. ¹H NMR(CDCl₃): δ 7.19(1H, s),7.20-7.28 1235, 931cm⁻¹. ¹H NMR(d₆-acetone): δ 10.6(1H, br (2H, m),7.38(1H, m), 7.41(1H, m), 7.47(1H, d, J=3Hz), s), 9.0-10.0(2H, br),7.59(1H, d, J=2.4Hz), 7.52 8.94(1H, br s). ¹³C NMR(CDCl₃): δ 107.2,112.0, (1H, d, J=8.1Hz), 7.44(1H, d, J=8.1Hz), 7.11(1H, 121.3, 122.0,123.3, 125.3, 129.8, 133.4, 135.8, 137.4, t, J=8.1Hz), 7.02(1H, t,J=8.1Hz), 6.01(1H, s); 138.5, 144.3, 177.5, 178.0. HRMS (EI) Calcd. For13_(C) NMR(d₆-acetone): δ 136.4, 127.6, 126.9, 121.9, C₁₄H₇Cl₂NO₂ [M⁺]:290.9854. Found: 290.9865. 121.5, 119.2, 112.1, 111.5, 104.7, 103.2.HRMS (FAB) Calculated for C₁₄H₉NO₄ [M⁺]: 255.0532. Found: 255.0529.2,5-Dichloro-3-(2-methyl-1H-indol-3-yl)-[1,4]benzoquinone 62%2,5-Dihydroxy-3-(2-metthyl-1H-indol-3-yl)- The residue was concentratedand purified by flash column [1,4]benzoquinone mp 222-223° C. IR(KBr):3392, chromatography using 15% EtOAc in hexane as eluent to 3313, 1630,1359, 1294, 1186cm⁻¹. ¹H NMR(d₆- afford pure2,5-dichloro-3-(2-methyl-1H-indol-3-yl)- acetone): δ 10.27(1H, br s),7.30(1H, d, J=8.1Hz), [1,4]benzoquinone (1.13 g, 97%)as a blue solid. mp158-159° C. 7.23(1H, d, J=8.1Hz), 7.02(1H, t, J=8.1Hz), R_(f) =0.35(3:7,EtOAc/hexane). ¹H NMR(CDCl₃)δ 6.94(1H, t, J=8.1Hz), 6.04(1H, s),2.32(3H, s). 8.40(bs, NH), 7.24-7.11(m, 5H), 2.26(s, 3H). ¹H NMR ¹³CNMR(d₆-acetone): δ 136.0, 135.5, 128.6, 120.6, (d₆-acetone): δ 10.60(1H,br s), 7.39(1H, s), 7.36(1H, d, J=7.8Hz), 119.8, 119.0, 111.9, 110.5,103.4, 102.2, 12.8. 7.24(1H, d, J=7.8Hz), 7.10(1H, t, J=7.8Hz), HRMS(FAB) Calcd. For C₁₅H₁₁NO₄ [M⁺]: 7.01(1H, t, J=7.8Hz). ¹³C NMR(CDCl₃)δ177.7, 176.6, 269.0688. Found: 269.0691. 144.3, 139.8, 139.3, 136.9,135.1, 133.1, 126.6, 122.0, 120.5, 119.6, 110.8, 104.8, 13.9. IR(KBr):3388, 3061, 1676, 1566, 1459, 1250, 1032, 749cm⁻¹. Anal. Calcd. forC₁₅H₉Cl₂NO₂: C, 58.85; H, 2.96; Cl, 23.16; N, 4.58. Found: C, 58.85; H,2.96; Cl, 23.16; N, 4.58. HRMS (EI) Calcd. For C₁₅H₉Cl₂NO₂ [M⁺]:305.0010. Found: 305.0002. 2,5-Dichloro-3-(2,5-dimethyl-1H-indol-3-yl)-73% 2,5-Dihydroxy-3-(2,5dimethyl-1H-indol-3-yl)- [1,4]benzoquinone[1,4]benzoquinone Blue crystals from benzene/hexane. mp 185-186° C. IRGreen crystals from benzene/hexane. mp 231-232° C. (KBr): 3346, 2922,1671, 1656, 1559, 1259cm⁻¹. ¹H NMR IR(KBr): 3416, 3287, 2917, 2858,1619, 1355, (CDCl₃): δ 2.32(3H, s), 2.41(3H, s), 6.94(1H, m), 6.971184cm⁻¹, ¹H NMR(d₆-acetone): δ 10.12(1H, br s), (1H, m), 7.18(1H, dd,J=0.6, 8.4Hz), 7.21(1H, s), 8.19 9.0-10.0(2H, br), 7.18(1H, d, J=8.1Hz),7.01(1H, (1H, br s). ¹³C NMR(CDCl₃): δ 14.3, 21.9, 104.8, 110.7, s),6.85(1H, d, J=8.4Hz), 6.04(1H, s), 2.33(3H, 119.8, 123.9, 127.2, 130.3,133.4, 133.7, 137.1, 139.8, s), 2.29(3H, s). ¹³C NMR(d₆-acetone): δ135.5, 140.1, 144.7, 177.0, 178.1. Anal. Calcd. for C₁₆H₁₁Cl₂NO₂: 134.4,128.8, 127.6, 122.1, 119.6, 110.2, 103.4, C, 60.02; H, 3.46; N, 4.37.Found: C, 59.80; H, 3.58; N, 101.7, 21.1, 12.8, HRMS (FAB) Calcd. For4.43. C₁₆H₁₃NO₄ [M⁺]: 283.0845. Found: 283.0846.2,5-Dichloro-3-(5-methoxy-2-methyl-1H-indol-3-yl)- 81%2,5-Dihydroxy-3-(5-methoxy-2-methyl-1H-indol-3- [1,4]benzoquinoneyl)-[1,4]benzoquinone Blue crystals from benzene/hexane. mp 199.2-199.5°C. IR mp 212° C. (dec). IR (KBr): 3389, 3080, 2925, 1612, (KBr): 3357,2938, 2895, 2820, 1672, 1645, 1565, 1275, 1484, 1358, 1329, 1198,799cm⁻¹. ¹H NMR(d₆- 1253cm⁻¹. ¹H NMR(CDCl₃): δ 2.28(3H, s), 3.78(3H, s),acetone): δ 10.10(1H, br s), 9.0-9.8(2H, br), 7.16 6.58(1H, d, J=2.4Hz),6.80(1H, dd, J=2.4, 9Hz), 7.17 (1H, d, J=6.6Hz), 6.75(1H, s), 6.65(1H,J=6.6Hz), (1H, d, J=9Hz), 7.22(1H, s), 8.22(1H, br s). ¹³C NMR 6.00(1H,s), 3.70(3H, s), 2.26(3H, s). ¹³C (CDCl₃): δ 14.4, 56.2, 102.5, 105.1,111.8, 112.2, 127.5, NMR(d₆-acetone): δ 154.1, 136.2, 131.0, 129.1,130.4, 133.4, 137.8, 139.7, 139.9, 144.7, 154.9, 176.9, 112.0, 111.0,110.4, 103.3, 102.3, 102.1, 55.1, 12.7. 178.1. HRMS (EI) Calcd. ForC₁₆H₁₁Cl₂NO₂ [M⁺]: HRMS (FAB) Calculated for C₁₆H₁₃NO₅ [M⁺]: 335.0116.Found: 335.0123. 299.0794. Found: 299.0795.2,5-Dichloro-3-(5-chloro-2-methyl-1H-indol-3-yl)- 87%2,5-Dihydroxy-3-(5-chloro-2-methyl-1H-indol-3-yl)- [1,4]benzoquinone[1,4]benzoquinone Blue crystals from benzene/hexane. mp 254-255° C. IRmp 230° C. (dec). IR(KBr): 3440, 3315, 1632, 1470, (KBr): 3336, 3078,1678, 1656, 1570, 1275cm⁻¹. ¹H NMR 1358, 1184, 795cm⁻¹. ¹HNMR(d₆-acetone): δ 10.43 (d₆-acetone): δ 2.36(3H, s), 7.07(1H, dd,J=2.1, 8.7Hz), (1H, br s), 9.0-10.0(2H, br), 7.28(1H, d, J=6.3Hz),7.30(1H, d, J=2.1Hz), 7.38(1H, dd, J=0.6, 8.7Hz), 7.39 7.23(1H, d,J=1.5Hz), 6.98(1H, dd, J=6.3, (1H, s), 10.9(1H, br s). ¹³CNMR(d₆-acetone): δ 13.0, 1.5Hz), 6.00(1H, s), 2.29(3H, s). ¹³C NMR(d₆-104.7, 112.4, 119.1, 121.4, 125.1, 128.7, 133.4, 134.5, acetone): δ137.5, 134.5, 129.7, 124.3, 120.5, 119.2, 139.1, 139.3, 140.5, 144.2,176.9, 178.1. Calculated for 111.9, 111.0, 103.4, 12.6. HRMS (FAB)Calculated C₁₅H₈Cl₃NO₂: C, 52.90; H, 2.37; N, 4.11; Found: C, 52.79; forC₁₇H₁₃NO₄ [M⁺]: 303.0298. Found: 303.0302. H, 2.44; N, 3.97.2,5-Dichloro-3-(2-cyclopropyl-1H-indol-3-yl)- 81%2,5-Dihydroxy-3-(2-cyclopropyl-1H-indol-3-yl)- [1,4]benzoquinone[1,4]benzoquinone This compound was synthesized according to the generalmp 179-180° C. IR(KBr): 3358, 2921, 1632, 1461, procedure A from2-cyclopropyl-1H-indole (100 mg, 0.636 mmol) 1364, 1187, 955, 741cm⁻¹.¹H NMR(d₆-acetone): δ and 2,5-dichloro-1,4-benzoquinone (225 mg, 1.27mmol) 10.0(1H, br s), 9.2-10.0(2H, br), 7.27(1H, d, J=7.8Hz), andobtained as a blue solid (200 mg, 95%). mp 181-182° C. 7.21(1H, d,J=7.8Hz), 7.01(1H, t, J=7.8Hz), R_(f) =0.37(3:7, EtOAc/hexane). ¹HNMR(CDCl₃): δ 6.93(1H, t, J=7.8Hz), 6.05(1H, s), 1.99 8.32(1H, br s),7.09-7.23(5H, m), 1.87(1H, m), 0.93(2H, (1H, m), 0.89(4H, m). ¹³CNMR(d₆-acetone): δ m), 0.70(2H, m). ¹³C NMR(CDCl₃)δ 177.8, 176.4, 144.3,140.5, 135.7, 128.6, 120.7, 119.4, 119.1, 111.9, 141.9, 139.6(2C),134.7, 133.0, 126.6, 122.1, 120.5, 119.5, 110.7, 103.5, 102.6, 9.2, 7.1.HRMS (FAB) 110.9, 105.3, 9.4, 7.3. IR(KBr): 3450, 3386, 3061, 1676,Calculated for C₁₇H₁₃NO₄ [M⁺]: 295.0845. Found: 1650, 1561, 1448, 1273,1241, 1032, 882, 745cm⁻¹. Anal. 295.0846. Calcd. for C₁₇H₁₁Cl₂NO₂ : C,61.47; H, 3.34; N, 4.22; Found: C, 61.71; H, 3.36; N, 4.20.2,5-Dichloro-3-(2-phenyl-1H-indol-3-yl)-[1,4]benzoquinone 65%2,5-Dihydroxy-3-(2-phenyl-1H-indol-3-yl)- Blue crystals frombenzene/hexane. mp 170-171° C. ¹H [1,4]benzoquinone NMR(CDCl₃): δ7.20(1H, m), 7.21(1H, s), 7.28-7.31(2H, Green crystals frombenzene/hexane. mp 227-228° C. m), 7.36-7.43(5H, m), 7.47(1H, m),8.61(1H, br s). ¹³C ¹H NMR(d₆-acetone): δ 10.8(1H, br s), 9.0-10.0NMR(CDCl₃): δ 104.7, 111.9, 120.4, 121.3, 123.3, 127.3, (2H, br),7.67(2H, m), 7.45(1H, m), 7.38(3H, m), 127.5, 129.1, 129.4, 132.4,133.4, 136.2, 139.6, 140.5, 7.29(1H, m), 7.12(1H, t, J=8.4Hz), 7.03(1H,t, J=7.2Hz), 141.3, 144.7, 176.5, 177.8. IR(KBr): 3384, 3056, 1683,6.06(1H, s). ¹³C NMR(d₆-acetone): δ 1565, 1446, 1248cm⁻¹. Anal. Calcd.for C₂₀H₁₁Cl₂NO₂: C, 137.0, 136.7, 133.7, 129.1, 128.8, 127.7, 127.2,65.24; H, 3.01; N, 3.73. Found: C, 64.61; H, 3.14; N, 3.76. 122.1,120.3, 119.6, 112.1, 111.4, 103.8, 102.3. IR (KBr): 3422, 3303, 3051,1629, 1355, 1296cm⁻¹. HRMS (FAB) Calcd. For C₂₀H₁₃NO₄ [M⁺]: 331.0845.Found: 331.0846.2,5-Dichloro-3-(1-methyl-1H-indol-3-yl)-[1,4]benzoquinone 62%2,5-Dihydroxy-3-(1-methyl-1H-indol-3-yl)- Blue crystals frombenzene/hexane. mp 156.1-156.2° C. IR [1,4]benzoquinone (KBr): 3142,3057, 2911, 1683, 1656, 1559, 749cm⁻¹. ¹H Green crystals frombenzene/hexane. mp 201-202° C. NMR(CDCl₃): δ 3.91(3H, s), 7.21(1H, s),7.23(1H, m), IR(KBr): 3286, 1627, 1533, 1355, 1298, 1234, 7.31(1H, m),7.39(1H, d, J=9.3Hz), 7.40(1H, dd, J=0.9, 1188, 935, 735cm⁻¹. ¹HNMR(d₆-acetone): δ 9.0-10.0 6.9Hz). ¹³C NMR(CDCl₃): δ 33.9, 105.6,110.3, 121.1, (2H, br)7.52(1H, d, J=8.1Hz), 7.49(1H, s), 122.3, 122.9,126.0, 133.5, 134.4, 137.0, 138.4, 144.1, 7.41(1H, d, J=8.4Hz), 7.19(1H,t, J=7.5Hz), 178.0. Anal. Calcd. for C₁₅H₉Cl₂NO₂: C, 58.85; H, 2.97; N,7.05(1H, t, J=7.5Hz),, 6.01(1H, s), 3.89(3H, s). 4.58. Found: C, 58.69;H, 3.07; N, 4.57. ¹³C NMR(d₆-acetone): δ 137.0, 131.6, 127.4, 122.2,121.5, 119.2, 111.8, 109.5, 103.6, 103.2, 32.4. HRMS (FAB) Calculatedfor C₁₅H₁₁NO₄ [M⁺]: 269.0688. Found: 269.0681.2,5-Dichloro-3-(2-ethyl-1H-indol-3-yl)-[1,4]benzoquinone 77%2,5-Dihydroxy-3-(2-ethyl-1H-indol-3-yl)- This compound was synthesizedaccording to the general [1,4]benzoquinone procedure A from2-ethyl-1H-indole(100 mg, 0.689 mmol) Green crystals frombenzene/hexane. mp 157-158° C. and 2,5-dichloro-1,4-benzoquinone(244 mg,1.38 mmol) IR(KBr): 3395, 3320, 3062, 2976, 1629, 1361, and was obtainedas a blue solid(209 mg, 95%). mp 143-144° C. 1291, 1173cm⁻¹. ¹HNMR(d₆-acetone): δ 10.27(1H, R_(f) =0.38(3:7, EtOAc/hexane). ¹HNMR(CDCl₃): δ br s), 9.0-10.0(2H, br), 7.31(1H, d, J=7.8Hz), 7.228.48(bs, NH), 7.29(m, 1H), 7.20(s, 1H), 7.19-7.08(m, (1H, d, J=7.8Hz),6.94-7.08(2H, m), 6.04(1H, s), 3H), 2.61(qd, J=7.5, 3.0Hz, 2H), 1.27(t,J=7.5Hz, 3H); 2.68(2H, q, J=7.8Hz), 1.28(3H, t, J=6.9Hz). ¹³C ¹HNMR(d₆-acetone): δ 10.62(1H, br s), 7.40(1H, s), 7.38 NMR(d₆-acetone): δ140.8, 136.2, 128.4, 120.7, (1H, d, J=8.1Hz), 7.24(1H, d, J=8.1Hz),7.09(1H, t, J=8.1Hz), 119.8, 119.0, 111.8, 110.7, 103.5, 101.1, 20.9,13.4. 8.1Hz), 7.01(1H, t, J=8.1Hz), 7.71(2H, q, J=7.8Hz), HRMS (FAB)Calcd. For C₁₆H₁₃NO₄ [M⁺]: 1.30(3H, t, J=7.8). ¹³C NMR(CDCl₃): δ 177.7,176.6, 283.0845. Found: 283.0846. 144.3, 142.1, 140.2, 139.5, 135.2,133.0, 126.4, 121.9, 120.5, 119.6, 110.9, 103.7, 21.2, 13.4. IR(KBr):3394, 3050, 2973, 1677, 1646, 1563, 1447, 1241, 1038, 746cm⁻¹. Anal.Calcd. for C₁₆H₁₁Cl₂NO₂: C, 60.02; H, 3.46; Cl, 22.15; N, 4.37. Found.C, 59.99; H, 3.51; N, 4.18. 2,5-Dichloro-3-(2-isopropyl-1H-indol-3-yl)-80% 2,5-Dihydroxy-3-(2-isopropyl-1H-indol-3-yl)- [1,4]benzoquinone[1,4]benzoquinone This compound was synthesized according to the generalmp 140° C.(dec). IR(KBr): 3352, 3290, 2926, 1627, procedure A from2-isoprenyl-1H-indole(50 mg, 0.314 mmol) 1363, 1306, 1189, 955, 744cm⁻¹.¹H NMR(d₆- and 2,5-dichloro-1,4-benzoquinone(111 mg, 0.629 mmol)acetone): δ 10.29(1H, br s), 9.0-10.0(2H, br), 7.31 and was obtained asa blue solid(74 mg, 70%). mp (1H, d, J=7.8Hz), 7.21(1H, d, J=7.8Hz),7.02(1H, 187-188° C. R_(f) =0.26(1:4, EtOAc/hexane). ¹H NMR t, J=7.8Hz),6.93(1H, t, J=7.8Hz), 6.05(1H, s), (CDCl₃)δ 8.40(bs, NH), 7.36(m, 1H),7.22(s, 1H), 7.21-7.08 3.03(1H, m), 1.32(6H, d, J=6.9Hz). ¹³C NMR(d₆-7.08(m, 3H), 2.88(septet, J=6.9Hz, 1H), 1.35(d, J=6.9Hz, acetone): δ144.7, 136.3, 128.3, 120.7, 119.7, 118.9, 3H), 1.27(d, J=6.9Hz, 3H). ¹³CNMR(CDCl₃)δ 111.9, 110.8, 103.5, 100.1, 27.3, 22.2. HRMS (FAB) 177.7,176.6, 145.8, 144.4, 140.9, 139.7, 135.1, 133.1, Calculated forC₁₇H₁₅NO₄ [M⁺]: 297.1001. Found: 126.1, 122.0, 120.4, 119.5, 111.0,102.6, 27.4, 22.9, 22.3. IR 297.0997. (KBr): 3421, 3312, 3053, 2963,1671, 1569, 1440, 1241, 1031, 759cm⁻¹. HRMS (EI) Calcd. For C₁₇H₁₃Cl₂NO₂[M⁺]: 333.0323. Found: 333.03132,5-Dichloro-3-(2-tert-butyl-1H-indol-3-yl)- 52%2,5-Dihydroxy-3-(2-tert-butyl-1H-indol-3-yl)- [1,4]benzoquinone[1,4]benzoquinone mp 235-236° C. IR(KBr)3419, 3317, 3059, 2965, 1673, mp195° C.(dec). IR(KBr): 3434, 3329, 2963, 1634, 1585, 1462, 1245, 1029,742cm⁻¹. ¹H NMR(d6-acetone): δ 1597, 1365, 1239, 944, 745cm⁻¹. ¹HNMR(d6- 10.40(1H, br s), 7.47(1H, s), 7.35(1H, d, J=7.8Hz), acetone): δ10.13(1H, br s), 8.8-9.8(2H, br), 7.27 7.23(1H, d, J=7.8Hz), 7.08(1H, t,J=7.8Hz), 6.95(1H, t, (1H, d, J=6.0Hz), 7.14(1H, d, J=6.0Hz), 6.99(1H,J=7.8Hz), 1.38(9H, s). ¹³C NMR(CDCl₃): δ 178.0, 177.7, t, J=6.0Hz),6.88(1H, t, J=6.0Hz), 6.05(1H, s), 145.3, 145.1, 143.2, 142.7, 134.9,133.5, 127.1, 122.6, 1.34(9H, s). ¹³C NMR(d₆-acetone): δ 145.2, 135.6,120.6, 118.3, 111.1, 102.1, 33.6, 30.5. HRMS (EI) Calcd. 129.3, 121.0,118.9, 118.5, 113.8, 110.7, 103.8, 99.5, For C₁₈H₁₅Cl₂NO₂ [M⁺]:347.0480. Found: 347.0491. 33.3, 29.7. HRMS (FAB) Calculated forC₁₇H₁₃NO₄ [M⁺]: 311.1158. Found: 311.11582,5-Dichloro-3-[2-(1-methyl-cyclopropyl)-1H-indol-3-yl]- 87%2,5-Dihydroxy-3-[2-(1-methyl-cyclopropyl)-1H- [1,4]benzoquinoneindol-3-yl]-[1,4]benzoquinone Blue needles from benzene/hexane. mp170-171° C. ¹H The solution was concentrated and purified by flashNMR(d₆-acetone): 0.53-0.60(1H, m), 0.64-0.70(1H, m), columnchromatography(oxalic acid-coated silica 0.70-0.77(1H, m), 0.92-0.98(1H,m), 1.48(3H, s), 7.01 gel)using 30% EtOAc in hexane as the eluent to(1H, dt, J=1.2, 7.5Hz), 7.10(1H, dt, J=1.2, 7.5Hz), 7.24 afford2,5-dihydroxy-3-[2-(1-methyl-cyclopropyl)- (1H, dd, J=0.6, 7.2Hz),7.37(1H, d, J=7.8Hz), 7.39(1H, 1H-indol-3-yl]-[1,4]benzoquinone(0.044 g,87%)as s), 10.70(1H, s). ¹³C NMR(d₆-acetone): 13.3, 14.1, 15.1, darkblue needles from acetone/hexane. mp 103° C. 24.5, 103.6, 111.4, 119.7,119.9, 121.9, 126.8, 133.8, 136.0, (dec). ¹H NMR(d₆-acetone):0.55-0.62(2H, m), 140.4, 140.8, 143.9, 144.0, 177.1, 177.9. IR(KBr):3409, 0.81-0.87(2H, m), 1.45(3H, s), 6.08(1H, s), 6.93 3059, 3004, 2966,2927, 1662, 1620, 1567, 1435, 1270, (1H, dt, J=0.9, 8.1Hz), 7.04(1H, dt,J=1.2, 8.1Hz), 1241, 1028, 755cm⁻¹. Anal. Calcd. for C₁₈H₁₃Cl₂NO₂: C,7.22(1H, d, J=7.8Hz), 7.31(1H, dd, J=0.9, 62.45; H, 3.78; N, 4.05.Found: C, 62.30; H, 3.77; N, 3.94. 8.1Hz), 9.0-10.1(2H, br s), 10.34(1H,br s). ¹³C NMR(d₆-acetone): 13.3, 14.8, 24.4, 101.4, 103.6, 110.8,112.3, 119.0, 119.5, 121.1, 128.4, 135.8, 142.2. IR(KBr): 3300, 3077,2958, 2924, 1640, 1360, 1190, 746cm⁻¹. HRMS (EI): calculated forC₁₈H₁₅NO₄ 309.1001; found 309.0999.2,5-Dichloro-3-[2-(1-methyl-cyclohexyl)-1H-indol-3-yl]- 90%2,5-Dihydroxy-3-[2-(1-methyl-cyclohexyl)-1H- [1,4]benzoquinoneindol-3-yl]-[1,4]benzoquinone Blue needles from benzene/hexane. mp184-185° C. ¹H Dark blue needles from acetone/hexane. mp 191-192° C.NMR(d₆-acetone): 1.36(3H, s), 1.38-1.66(10H, m), 6.96 ¹HNMR(d₆-acetone): 1.34(3H, s), 1.25-1.60 (1H, dt, J=1.2, 7.2Hz), 7.08(1H,dt, J=1.2, 7.2Hz), 7.23 (10H, m), 6.08(1H, s), 6.90(1H, dt, J=1.2,6.9Hz), (1H, d, J=7.8Hz), 7.37(1H, d, J=8.1Hz), 7.45(1H, s), 7.02(1H,dt, J=1.2, 7.2Hz), 7.17(1H, d, J=7.8Hz), 10.39(1H, br s). ¹³CNMR(d₆-acetone): 22.6, 22.8, 26.2, 7.32(1H, dt, J=0.9, 8.1Hz),8.5-10.0(2H, br 27.4, 37.5, 37.8, 38.2, 102.4, 111.2, 118.5, 119.5,121.5, s), 10.12(1H, br s). ¹³C NMR(d₆-acetone): 23.0, 127.4, 134.0,135.6, 142.4, 142.8, 143.9, 145.0, 177.8. IR 26.3, 37.6, 37.8, 100.4,103.8, 110.7, 113.8, 118.5, (KBr): 3421, 3320, 3054, 2936, 2863, 1672,1618, 1573, 118.8, 120.9, 129.4, 135.6, 143.8. IR(KBr): 3270, 1515,1457, 1205, 1024cm⁻¹. Anal. Calcd. for 2975, 2932, 2862, 1700, 1535,1465, 938, 717cm⁻¹. C₂₁H₁₉Cl₂NO₂: C, 64.96; H, 4.93; N, 3.61. Found: C,65.04; HRMS (EI): calcd. for C₂₁H₂₁NO₄ 351.1471, found H, 4.89; N, 3.63.351.1471. 3-(4-Fluoro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 65%3-(4-Fluoro-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 161-162° C. ¹H [1,4]benzoquinone NMR(d₆-acetone):6.79(1H, ddd, J=0.7, 7.6, 11.2Hz), Dark blue needles fromacetone/hexane. mp 248° C. 7.15(1H, dt, J=5.2, 7.6Hz), 7.34(1H, d,J=8Hz), 7.38 (dec). ¹H NMR(d₆-acetone): 6.04(1H, s), 6.70(1H, (1H, s),7.66(1H, d, J=2.8Hz), 11.15(1H, s). ¹³C NMR dd, J=7.8, 11.1Hz), 7.09(1H,dt, J=5.1, 8.1Hz), (d₆-acetone): 104.5, 105.7, 105.9, 108.6, 123.1,123.2, 7.28(1H, dd, J=3.3, 8.1Hz), 7.43(1H, d, J=2.4Hz), 129.2, 133.6,139.1, 143.6, 154.9, 157.2, 177.5 177.8. IR 8.0-10.4(2H, br s),10.76(1H, br s). ¹³C NMR (KBr): 3386, 3067, 1671, 1577, 1505, 1422,1318, 1265, (d₆-acetone): 103.5, 104.6, 104.9, 108.0, 122.2, 1226,1019cm⁻¹. Anal. Calcd. for C₁₄H₆Cl₂FNO₂: C, 54.22; 122.3, 126.8, 139.4,155.0, 158.3. IR(KBr): 3452, H, 1.95; N, 4.52. Found: C, 54.15; H, 1.89;N, 4.58. 2954, 2852, 1661, 1639, 1359, 1232, 1192, 1035, 934cm⁻¹. HRMS(EI): calcd. for C₁₄H₈FNO₄ 273.0437, found 273.0436.3-(4-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 74%3-(4-Chloro-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 204-205° C. ¹H [1,4]benzoquinone NMR(d₆-acetone):7.07(1H, dd, J=0.8, 7.6Hz), 7.15(1H, Dark blue needles fromacetone/hexane. mp 230° C. t, J=7.6Hz), 7.40(1H, s), 7.49(1H, dd, J=0.8,8.0Hz), (dec). ¹H NMR(d₆-acetone): 6.05(1H, s), 7.01(1H, 7.60(1H, d,J=2.8Hz), 11.17(1H, br s). ¹³C NMR(d₆- dd, J=0.8, 7.6Hz), 7.10(1H, t,J=8.0Hz), 7.40 acetone): 106.3, 111.4, 121.0, 123.2, 124.4, 125.0,128.4, (1H, d, J=2.4Hz), 7.44(1H, dd, J=0.8, 8.0Hz), 133.6, 137.9,140.5, 140.9, 143.9, 177.7, 177.9. IR(KBr): 8.6-10.1(2H, br s),10.77(1H, br s)¹³C NMR(d₆- 3350, 3115, 3068, 1673, 1659, 1572, 1416,1274, 1196, acetone): 103.6, 104.0, 110.9, 112.5, 120.4, 122.3,1023cm⁻¹. Anal. Calcd. for C₁₄H₆Cl₃NO₂: C, 51.49; H, 124.9, 125.6,127.2, 138.1. IR(KBr): 3324, 2953, 1.85. Found: C, 51.33; H, 2.00. 1628,1536, 1484, 1424, 1353, 1187, 927cm⁻¹. HRMS (FAB) : calcd. forC₁₄H₈ClNO₄ 289.0142, found 289.0143.3-(4-Bromo-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 86%3-(4-Bromo-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 247-248° C. ¹H [1,4]benzoquinone NMR(d₆-acetone):7.09(1H, t, J=8.0Hz), 7.25(1H, dd, J=0.8, Dark blue needles fromacetone/hexane. mp 232° C. 8.0Hz), 7.41(1H, s), 7.54(1H, dd, J=0.8,8.0Hz), (dec). ¹H NMR(d₆-acetone): 6.06(1H, s), 7.04(1H, 7.60(1H, d,J=3.2Hz), 11.11(1H, br s). ¹³C NMR(d₆- t, J=8.0Hz), 7.20(1H, dd, J=0.8,8.0Hz), 7.41 acetone): 107.3, 111.2, 111.9, 113.1, 123.5, 124.3, 126.0,(1H, d, J=2.8Hz), 7.50(1H, dd, J=0.8, 8.0Hz), 128.2, 133.6, 137.7,141.0, 144.1, 177.6, 177.9. IR(KBr): 9.0-10.0(2H, br s), 10.77(1H, brs). ¹³C NMR(d₆- 3367, 3116, 3068, 1651, 1613, 1570, 1517, 1480, 1412,acetone): 103.6, 104.9, 111.4, 113.7, 122.7, 123.7, 1021, 875cm⁻¹. Anal.Calcd. for C₁₄H₆BrCl₂NO₂: C, 45.32; 126.3, 127.2, 127.3, 137.8. IR(KBr).3326, 2983, H, 1.63. Found: C, 45.38; H, 1.84. 2854, 1629, 1540, 1341,1187, 934cm⁻¹. HRMS (EI): calcd. for C₁₄H₈BrNO₄ 332.9637, found332.9634. 2,5-Dichloro-3-(4-methoxy-1H-indol-3-yl)- 82%2,5-Dihydroxy-3-(4-methoxy-1H-indol-3-yl)- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 195-196° C. ¹HDark green needles from acetone/hexane. mp 225° C. NMR(d₆-acetone):3.76(1H, s), 6.58(1H, dd, J=3.6, 5.1Hz), (dec). ¹H NMR(d₆-acetone):3.71(3H, s), 6.00(1H, 7.11(1H, s), 7.12(1H, d, J=1.5Hz), 7.35(1H, s),7.56 s), 6.48(1H, dd, J=3.2, 5.6Hz), 7.03(1H, d, J=2.0Hz), (1H, d,J=3Hz), 10.86(1H, br s). ¹³C NMR(d₆-acetone): 7.04(1H, s), 7.23(1H, d,J=2.8Hz), 8.5-9.8 55.0, 101.2, 105.4, 106.5, 123.6, 126.8, 127.0, 133.2,136.4, (2H, br s), 10.42(1H, br s). ¹³C NMR(d₆-acetone): 138.0, 141.9,143.6, 153.3, 177.6, 177.8. IR(KBr): 3324, 54.9, 100.2, 103.2, 103.7,105.0, 113.9, 118.2, 122.6, 3042, 2967, 1676, 1638, 1546, 1486, 1260,1229, 1009cm⁻¹. 124.6, 138.2, 154.3. IR(KBr): 3314, 2958, 2933, Anal.Calcd. for C₁₅H₉Cl₂NO₃: C, 55.93; H, 2.82; N, 4.35. 1634, 1511, 1357,1200, 1089, 936cm⁻¹. HRMS Found: C, 56.09; H, 2.87; N, 4.32. (EI):calcd. for C₁₅H₁₁NO₅ 285.0637, found 285.0635.3-(4-Benzyloxy-1H-indol-3-yl)-2,5-dichloro- 81%3-(4-Benzyloxy-1H-indol-3-yl)-2,5-dihydroxy- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 193-194° C. ¹HDark green needles from acetone/hexane. mp 188-189° C. NMR(d₆-acetone):5.01(2H, s), 6.64(1H, dd, J=2.4, 6.4Hz), ¹H NMR(d₆-acetone): 5.03(2H,s), 5.88 7.06(1H, s), 7.4-7.7(2H, m), 7.23-7.34(5H, m), 7.45 (1H, s),6.60(1H, dd, J=1.6, 7.2Hz), 7.06(1H, q, J=8.4Hz), (1H, d, J=2.8Hz),10.79(1H, br s). ¹³C NMR(d₆-acetone): 7.07(1H, d, J=2.8Hz), 7.21(1H, d,J=2.4Hz), 70.3, 102.1, 105.6, 106.3, 117.8, 123.5, 126.3, 127.8, 128.0,7.24-7.32(3H, m), 7.34(1H, d, J=1.6Hz), 128.6, 132.9, 137.5, 138.1,141.7, 143.8, 152.7, 177.2, 7.36(1H, d, J=2.0Hz), 8.8-9.8(2H, br s),10.44 177.8. IR(KBr): 3346, 3116, 3063, 3034, 1673, 1656, 1572, (1H, brs). ¹³C NMR(d₆-acetone): 69.7, 101.1, 103.0, 1508, 1453, 1423, 1270cm⁻¹.Anal. Calcd. for 103.7, 105.2, 113.8, 118.3, 122.6, 124.5, 127.2,C₂₁H₁₃Cl₂NO₃: C, 63.34; H, 3.29. Found: C, 63.26; H, 3.40. 127.6, 128.4,137.9, 138.3, 153.4. IR(KBr): 3396, 3308, 2918, 2869, 1628, 1506, 1443,1318, 1075cm⁻¹. HRMS (EI): calcd. for C₂₁H₁₅NO₅ 361.0950, found361.0952. 2,5-Dichloro-3-(4-methyl-1H-indol-3-yl)-[1,4]benzoquinone 81%2,5-dihydroxy-3-(4-methyl-1H-indol-3-yl)- Blue needles frombenzene/hexane. mp 192-193° C. ¹H [1,4]benzoquinone NMR(d₆-acetone):2.28(3H, s), 6.83(1H, dt, J=0.6, 5.4Hz), Dark green needles fromacetone/hexane. mp 220° C. 7.06(1H, t, J=5.7Hz), 7.32(1H, d, J=6Hz),7.39 (dec). ¹H NMR(d₆-acetone): 2.36(3H, s), 6.05(1H, (1H, s), 7.44(1H,d, J=2.1Hz), 10.77(1H, br s). ¹³C NMR s), 6.76(1H, dt, J=0.9, 6.9Hz),7.00(1H, t, J=7.6Hz), (d₆-acetone): 19.3, 107.1, 110.0, 122.0, 122.5,126.1, 127.1, 7.23(1H, d, J=2.4Hz), 7.27(1H, d, J=8.1Hz), 129.8, 133.8,136.9, 140.4, 142.0, 143.7, 177.9, 178.3. IR 8.5-10.2(2H, br s),10.41(1H, br s). ¹³C NMR (KBr): 3369, 3114, 3068, 1669, 1553, 1511,1267, 1182, (d₆-acetone): 18.7, 103.7, 104.4, 109.6, 114.1, 121.0, 1019,876, 753cm⁻¹ . Anal. Calcd. for C₁₅H₉Cl₂NO₂: C, 121.7, 125.6, 126.8,130.1, 136.9. IR(KBr): 3417, 58.85; H, 2.96. Found: C, 58.85; H, 2.91.3328, 3128, 2959, 2927, 2861, 1628, 1533, 1357, 934cm⁻¹. HRMS (EI):calcd. for C₁₅H₁₁NO₄ 269.0688, found 269.0688.3-(5-Fluoro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 72%3-(5-Fluoro-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 175-176° C. ¹H [1,4]benzoquinone NMR(d₆-acetone):7.00(1H, dt, J=2.1, 9.0Hz), 7.16(1H, Dark blue needles fromacetone/hexane. mp 225-226° C. dd, J=1.2, 10.2Hz), 7.35(1H, s), 7.53(1H,dd, J=4.5, 8.7Hz), ¹H NMR(d₆-acetone): 6.03(1H, s), 6.93(1H, dt,7.79(1H, d, J=2.7Hz), 11.1(1H, br s). ¹³C NMR(d₆- J=2.4, 9.2Hz),7.26(1H, dd, J=2.4, 6.4Hz), 7.44 acetone): 106.4, 106.7, 110.3, 110.7,113.2, 113.3, 132.2, (1H, dd, J=4.8, 8.8Hz), 7.69(1H, d, J=2.4Hz),133.0, 133.3, 143.8, 156.5, 159.6, 177.4, 177.8. IR(KBr): 8.2-10.4(2H,br s), 10.69(1H, br s). ¹³C NMR(d₆- 3394, 3131, 3063, 2956, 2925, 1678,1656, 1570, 1423, acetone): 103.2, 106.6, 106.9, 109.5, 109.8, 112.3,1258, 1011cm⁻¹. Anal. Calcd. for C₁₄H₆Cl₂FNO₂: C, 54.22; 112.4, 129.6,133.0, 156.5, 158.8. IR(KBr): 3449, H, 1.95; N, 4.52. Found: C, 54.30;H, 2.01; N, 4.54. 3294, 2956, 2855, 1627, 1486, 1335, 1230, 1184,933cm⁻¹. HRMS (EI): calcd. for C₁₄H₈FNO₄ 273.0437, found 273.0442.3-(5-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 62%3-(5-Chloro-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 189-190° C. ¹H [1,4]benzoquinone NMR(CDCl₃): 7.24(1H,s), 7.25(1H, dd, J=0.9, 2.1Hz), Dark blue needles from acetone/hexane.mp 192-193° C. 7.36(1H, d, J=0.9Hz), 7.37-7.39(1H, m), 7.58(1H, d,J=3Hz), ¹H NMR(d₆-acetone): 6.03(1H, s), 7.12(1H, dd, 8.60(1H, s). ¹³CNMR(d₆-acetone): 106.4, 113.6, J=2.1, 8.7Hz), 7.46(1H, d, J=8.7Hz),7.56(1H, d, 120.9, 122.4, 125.7, 127.2, 131.7, 133.4, 134.9, 137.5,J=1.8Hz), 7.67(1H, d, J=2.7Hz), 8.5-10.0(2H, 138.7, 143.9, 177.5, 177.9.IR(KBr): 3331, 3053, 1675, br s), 10.78(1H, br s). ¹³C NMR(d₆-acetone):103.2, 1652, 1568, 1505, 1460, 1274, 1247, 803cm⁻¹. Anal. Calcd. 104.6,111.3, 112.9, 121.3, 121.6, 124.6, 128.0, for C₁₄H₆Cl₃NO₂: C, 51.49; H,1.85; N, 4.29. Found: C, 129.3, 134.8. IR(KBr): 3409, 3302, 2917, 2879,51.51; H, 2.01; N, 4.26. 1631, 1529, 1354, 1231, 933cm⁻¹. HRMS (EI):calcd. for C₁₄H₈ClNO₄ 289.0142, found 289.0144.3-(5-Bromo-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 56%3-(5-Bromo-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 205-206° C. ¹H [1,4]benzoquinone NMR(d₆-acetone):7.31(1H, dd, J=2.0, 8.8Hz), 7.37(1H, Dark blue needles fromacetone/hexane. mp 210-211° C. s), 7.50(1H, d, J=8.4Hz), 7.62(1H, s),7.76(1H, d, J=2.8Hz), ¹H NMR(d₆-acetone): 6.02(1H, s), 7.24(1H, dd,11.14(1H, s). ¹³C NMR(d₆-acetone): 106.3, 113.3, J=1.8, 8.7Hz), 7.42(1H,d, J=8.7Hz), 7.65(1H, 114.0, 123.9, 125.0, 127.8, 131.5, 133.4, 135.2,137.5, d, J=2.7Hz), 7.71(1H, d, J=2.1Hz), 8.5-10.2(2H, 138.8, 143.9,177.5, 177.9. IR(KBr): 3382, 3138, 3058, br s), 10.82(1H, br s). ¹³CNMR(d₆-acetone): 103.2, 1671, 1650, 1571, 1457, 1271, 1245, 1113,1010cm⁻¹. Anal. 104.5, 112.2, 113.3, 124.2, 124.4, 128.6, 129.0, Calcd.for C₁₄H₆BrCl₂NO₂: C, 45.32; H, 1.63; N, 3.78. 129.1, 135.1 IR(KBr):3309, 3035, 1631, 1455, Found: C, 45.56; H, 1.77; N, 3.70. 1349, 1322,1230, 930cm⁻¹. HRMS (EI): calcd. for C₁₄H₈BrNO₄ 332.9637, found332.9636. 2,5-Dichloro-3-(5-hydroxy-1H-indol-3-yl)- 70%2,5-Dihydroxy-3-(5-hydroxy-1H-indol-3-yl)- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 101(dec)° C. ¹HDark green needles from acetone/hexane. mp 235° C. NMR(d₆-acetone):6.80(2H, m), 7.33(1H, s), 7.34(1H, m), (dec). ¹H NMR(d₆-acetone):6.00(1H, s), 6.73(1H, 7.65(1H, d, J=3.3Hz), 7.92(1H, br s), 10.86(1H, brs). dd, J=2.4, 8.7Hz), 6.92(1H, d, J=2.4Hz), 7.26 ¹³C NMR(d₆-acetone):103.7, 105.9, 106.2, 112.4, 112.6, (1H, d, J=8.7Hz), 7.51(1H, d,J=3.0Hz), 7.6-7.8 113.4, 113.8, 131.1, 131.1, 131.3, 133.4. IR(KBr):3500, (1H, br s), 8.0-10.0(2H, br s), 10.39(1H, br s). ¹³C 3121, 1698,1566, 1167, 1102, 851, 694, 617cm⁻¹. Anal. NMR(d₆-acetone): 103.1,104.0, 106.2, 111.7, 112.2, Calcd. for C₁₄H₇Cl₂NO₃: C, 54.57; H, 2.29.Found: C, 127.8, 128.0, 128.2, 131.1, 151.0 IR(KBr): 3302, 54.95; H,2.62. 1697, 1630, 1463, 1357, 1202, 935, 856, 802cm⁻¹. HRMS (EI): calcd.for C₁₄H₉NO₅ 271.0481, found 271.0482.2,5-Dichloro-3-(5-methoxy-1H-indol-3-yl)- 63%2,5-Dihydroxy-3-(5-methoxy-1H-indol-3-yl)- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 195-196° C. ¹HDark green needles from acetone/hexane. mp 178° C. NMR(CDCl₃): 6.78(1H,d, J=2.4Hz), 6.93(1H, dd, J=2.1, (dec). ¹H NMR(d₆-acetone): 6.01(1H, s),6.79(1H, 8.4Hz), 7.23(1H, s), 7.34(1H, d, J=9.0Hz), 7.54 dd, J=2.4,8.7Hz), 7.06(1H, d, J=2.4Hz), 7.33 (1H, d, J=3.0Hz), 8.62(1H, br s). ¹³CNMR(d₆-acetone): (1H, d, J=8.7Hz), 7.56(1H, d, J=3.0Hz), 8.5-10.0 55.2,103.8, 106.7, 112.4, 112.8, 126.5, 130.9, 131.0, 131.4, (2H, br s),10.47(1H, br s). ¹³C NMR(d₆-acetone): 133.4, 139.8, 143.7, 154.8, 177.8,178.0. IR(KBr): 3328, 55.1, 103.1, 104.0, 104.5, 111.8, 112.0, 127.4,128.2, 3043, 2924, 2855, 1675, 1638, 1543, 1484, 1260, 1227cm⁻¹. 131.5,154.1. IR(KBr): 3324, 3124, 3070, 3004, Anal. Calcd. for C₁₅H₉Cl₂NO₃: C,55.93; H, 2.82; N, 4.35. 2959, 2924, 2838, 1629, 1481, 1354, 1208cm⁻¹.Found: C, 55.72; H, 2.99; N, 4.24. HRMS (EI): calcd. for C₁₅H₁₁NO₅285.0637, found 285.0639. 3-(5-Benzyloxy-1H-indol-3-yl)-2,5-dichloro-63% 3-(5-Benzyloxy-1H-indol-3-yl)-2,5-dihydroxy- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 164-165° C.. ¹HDark green needles from acetone/hexane. mp 198° C. NMR(CDCl₃). 5.08(2H,s), 6.89(1H, s, J=2.1Hz), 7.01 (dec). ¹H NMR(d₆-acetone): 5.08(2H, s),6.01(1H, 1H, dd, J=2.4, 8.7Hz), 7.22(1H, s), 7.26(1H, s), 7.30-7.50 s),6.88(1H, dd, J=2.7, 8.7Hz), 7.20(1H, d, J=2.4Hz), (6H, m)7.53(1H, d,J=2.7Hz), 8.64(1H, br s). ¹³C NMR 7.37(1H, d, J=1.8Hz), 7.3-7.4(3H, m),7.48 (d₆-acetone): 70.5, 105.6, 106.6, 112.8, 113.0, 126.3, 126.6, (2H,d, J=6.6Hz), 7.58(1H, d, J=2.7Hz), 8.0-10.2 127.8, 128.5, 131.0, 131.2,131.7, 133.4, 138.1, 139.2, (2H, br s), 10.50(1H, br s). ¹³CNMR(d₆-acetone): 143.8, 153.9, 177.7, 178.0. IR(KBr): 3342, 3065, 3037,70.5, 103.1, 104.6, 105.8, 112.0, 112.4, 127.4, 127.7, 2907, 2874, 1674,1564, 1480, 1426, 1258, 1009cm⁻¹. Anal. 127.8, 128.4, 128.5, 131.7,138.5, 158.3. IR(KBr): Calcd. for C₂₁H₁₃Cl₂NO₃: C, 63.34; H, 3.29; N,3.52. Found: 3110, 3035, 2919, 2866, 1632, 1479, 1358, 1195, C, 63.24;H, 3.42; N, 3.49. 1018, 930cm⁻¹. HRMS (EI): calcd. for C₂₁H₁₅NO₅361.0950, found 361.0951.2,5-Dichloro-3-(5-methyl-1H-indol-3-yl)-[1,4]benzoquinone 80%2,5-Dihydroxy-3-(5-methyl-1H-indol-3-yl)- Blue needles frombenzene/hexane. mp 176-177° C.. ¹H [1,4]benzoquinone NMR(d₆-acetone):2.40(3H, s), 7.02(1H, dd, J=1.8, 8.4Hz), Dark green needles fromacetone/hexane. mp 190° C. 7.20(1H, m), 7.33(1H, s), 7.40(1H, d,J=8.4Hz), (dec). ¹H NMR(d₆-acetone): 2.09(3H, s), 6.02(1H, 7.66(1H, dd,J=3.0Hz), 10.89(1H, br s). ¹³C NMR(d₆- s), 6.96(1H, dd, J=1.6, 8.4Hz),7.31(1H, s), 7.32 acetone): 21.27, 106.4, 111.9, 121.4, 123.9, 126.2,129.3, (1H, d, J=8.4Hz), 7.53(1H, d, J=2.8Hz), 8.2-10.2 130.6, 133.4,134.8, 136.4, 139.3, 143.6, 177.8, 177.9. IR (2H, br s), 10.46(1H, brs). ¹³C NMR(d₆-acetone): (KBr): 3367, 3069, 2919, 2859, 1657, 1654,1561, 1507, 21.1, 103.1, 104.2, 111.2, 112.2, 121.6, 123.1, 127.2, 1423,1248, 1111cm⁻¹. Anal. Calcd. for C₁₅H₉Cl₂NO₂: C, 127.7, 128.0, 134.8.IR(KBr): 3305, 3045, 1631, 58.85; H, 2.96. Found: C, 58.95; H, 3.14.1350, 1232, 1203, 932, 798cm⁻¹. HRMS (EI): calcd. for C₁₅H₁₁NO₄269.0688, found 269.0683.3-(6-Fluoro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 80%3-(6-Fluoro-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 168-169° C.. ¹H [1,4]benzoquinone NMR(d₆-acetone):6.95(1H, tt, J=1.8, 9Hz), 7.28(1H, dt, Dark green needles fromacetone/hexane. mp 130-131° C.. J=1.8, 9.6Hz), 7.37(1H, d, J=2.1Hz),7.40(1H, d, J=5.4, ¹H NMR(d₆-acetone): 6.03(1H, s), 6.85 8.7Hz),7.72(1H, d, J=2.4Hz), 11.12(1H, br s). ¹³C (1H, dt, J=2.4, 9.6Hz),7.19(1H, dd, J=2.4, 9.9Hz), NMR(d₆-acetone): 98.1, 98.4, 106.8, 108.6,108.9, 122.6, 7.51(1H, dd, J=5.4, 9.0Hz), 7.60(1H, d, J=2.7Hz), 122.7,131.0, 133.4, 143.8, 158.2, 161.4, 177.4, 177.9. IR 8.2-10.4(2H, br s),10.67(1H, br s). ¹³C (KBr): 3380, 3079, 2920, 1650, 1559, 1453, 1409,1235, NMR(d₆-acetone): 97.2, 97.6, 103.2, 107.5, 107.8, 1140, 1010,882cm⁻¹. Anal. Calcd. for C₁₄H₆Cl₂FNO₂: C, 122.9, 126.0, 123.6, 128.2,136.2, 158.1, 161.2. IR 54.22; H, 1.95. Found: C, 54.48; H, 2.06. (KBr):3350, 1626, 1528, 1454, 1361, 1235cm⁻¹. HRMS (EI): calcd. for C₁₄H₈FNO₄273.0437, found 273.0436.3-(6-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 71%3-(6-Chloro-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 182-183° C.. ¹H [1,4]benzoquinone NMR(CDCl₃):7.18(1H, dd, J=1.8, 8.7Hz), 7.23(1H, s), Dark green needles fromacetone/hexane. mp 229° C. 7.26(1H, s), 7.31(1H, d, J=8.7Hz), 7.44(1H,dd, J=0.6, (dec). ¹H NMR(d₆-acetone): 6.03(1H, s), 7.04(1H, 1.8Hz),7.54(1H, d, J=2.7Hz), 8.75(1H, br s). ¹³C NMR dd, J=1.8, 8.7Hz),7.50(1H, d, J=1.8Hz), 7.52 (d₆-acetone): 106.9, 112.0, 117.9, 120.7,122.8, 124.7, 1H, d, J=8.7Hz), 7.64(1H, d, J=2.4Hz), 8.4-10.4 127.7,131.3, 133.4, 136.8, 138.6, 143.8, 177.4, 177.8. IR (2H, br s),10.74(1H, br s). ¹³C NMR(d₆-acetone). (KBr): 3325, 3122, 3071, 2962,2926, 1673, 1564, 1517, 103.2, 105.0, 111.3, 111.4, 119.6, 123.2, 125.6,1449, 1401, 1020cm⁻¹. Anal. Calcd. for C₁₄H₆Cl₃NO₂: C, 127.0, 128.6,136.8. IR(KBr): 3418, 3305, 2956, 51.49; H, 1.85; N, 4.29. Found: C,51.77; H, 1.94; N, 4.21. 1623, 1534, 1451, 1357, 936cm⁻¹. HRMS (EI):calcd. for C₁₄H₈ClNO₄ 289.0142, found 289.0144.3-(6-Bromo-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 83%3-(6-Bromo-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 180° C.(dec). ¹H [1,4]benzoquinone NMR(d₆-acetone):5.15(2H, s), 6.90(1H, dd, J=2.4, 9.0Hz), Dark green needles fromacetone/hexane. mp 205° C. 7.14(1H, d, J=2.1Hz), 7.26-7.36(3H, m),7.39(2H, (dec). ¹H NMR(d₆-acetone): 5.14(2H, s), 6.01(1H, t, J=7.2Hz),7.50(2H, d, J=7.2Hz), 7.61(1H, d, J=2.4Hz), s), 6.80(1H, dd, J=2.4,8.7Hz), 7.07(1H, d, J=2.1Hz), 10.84(1H, br s). ¹³C NMR(d₆-acetone):70.2, 96.6, 7.26-7.58(9H, m), 8.4-10.2(2H, br s), 10.44 106.9, 111.1,120.4, 122.4, 122.9, 127.6, 127.8, 128.6, (1H, br s). ¹³CNMR(d₆-acetone): 70.2, 96.0, 103.1, 129.6, 129.8, 133.4, 137.2, 138.0,143.7, 155.8, 177.4, 104.7, 110.1, 121.5, 122.7, 126.7, 127.6, 127.7,177.9. IR(KBr): 3396, 3127, 3064, 2946, 2815, 1672, 1651, 128.5, 137.0,138.2, 155.4. IR(KBr): 3414, 3314, 1560, 1237, 1011, 819cm⁻¹. Anal.Calcd. for C₂₁H₁₃Cl₂NO₃: 2925, 1631, 1353, 1299, 1239, 1023, 935cm⁻¹. C,63.34; H, 3.29; N, 3.52. Found: C, 63.07; H, 3.43; N, HRMS (EI): calcd.for C₂₁H₁₅NO₅ 361.0950, found 3.45. 361.0951.2,5-Dichloro-3-(6-methyl-1H-indol-3-yl)-[1,4]benzoquinone 82%2,5-Dihydroxy-3-(6-methyl-1H-indol-3-yl)- This compound was synthesizedaccording to the general [1,4]benzoquinone procedure A from7-methyl-1H-indole(100 mg, 0.762 mmol) Dark green needles fromacetone/hexane. mp 190° C. and 2,5-dichloro-1,4-benzoquinone(270 mg,1.52 mmol) (dec). ¹H NMR(d₆-acetone): 2.37(3H, s), 5.97(1H, and wasobtained as a blue solid(188 mg, 81%). mp s), 6.84(1H, dd, J=1.6,8.4Hz), 7.20(1H, s), 7.38 169-170° C.. ¹H NMR(d₆-acetone): 2.39(3H, s),6.92(1H, (1H, d, J=8.4Hz), 7.48(1H, d, J=2.8Hz), 8.0-10.0 dd, J=0.8,4.4Hz), 7.25(1H, d, J=8.4Hz), 7.24-7.26(2H, (2H, br s), 10.45(1H, br s).¹³C NMR(d₆-acetone): m), 7.61(1H, d, J=2.8Hz), 10.92(1H, br s). ¹³CNMR(d₆- 21.0, 103.2, 104.6, 111.3, 112.3, 121.0, 121.7, 124.8, acetone):20.9, 106.6, 112.0, 121.5, 122.1, 123.8, 130.3, 127.1, 130.9, 136.8.IR(KBr): 3398, 2919, 2855, 131.9, 133.4, 136.2, 136.9, 139.2, 143.7,177.7, 178.0. IR 1701, 1617, 1530, 1452, 932cm⁻¹. HRMS (EI): (KBr):3409, 3065, 2918, 1652, 1557, 1256, 1236, 1116, calcd. for C₁₅H₁₁NO₄269.0688, found 269.0685. 1015, 878, 805cm⁻¹. Anal. Calcd. forC₁₅H₉Cl₂NO₂: C, 58.85; H, 2.96. Found: 58.94; H, 3.08.2,5-Dichloro-3-(7-propyl-1H-indol-3-yl)-[1,4]benzoquinone 66%2,5-Dihydroxy-3-(7-propyl-1H-indol-3-yl)- Blue needles frombenzene/hexane. mp 187-188° C.. R_(f) =0.31 [1,4]benzoquinone (3:7,EtOAc/hexane). ¹H NMR(CDCl₃)δ 8.70(bs, Green crystals frombenzene/hexane. mp 218-219° C.. NH), 7.55(d, J=3.0Hz, 1H), 7.32(m, 1H),7.21(s, 1H), IR(KBr): 3427, 3326, 1618, 1325, 1291, 1185cm⁻¹. 7.11(m,2H), 2.53(s, 3H). ¹H NMR(d₆-acetone): δ 10.95 ¹H NMR(d₆-acetone): δ10.58(1H, br s), 9.0-10.0 (1H, br s), 7.68(1H, m), 7.37(1H, m), 7.25(1H,m), 7.03 (2H, br), 7.56(1H, d, J=2.7Hz), 7.36(1H, t, J=4.5Hz), (2H, m),2.55(3H, s). ¹³C NMR(d₆-acetone): δ 178.0, 6.95(1H, s), 6.93(1H, s),6.02(1H, s), 177.7, 143.7, 139.3, 136.3, 135.9, 133.4, 130.0, 125.7,2.52(3H, s). ¹³C NMR(d₆-acetone): δ 135.8, 127.2, 122.9, 121.5, 120.5,119.4, 107.2, 16.2. IR(KBr): 3403, 126.6, 122.1, 120.6, 119.6, 119.5,112.2, 105.2, 3072, 1670, 1563, 1431, 1236, 1037, 750cm⁻¹. Anal. Calcd.103.2, 16.4. HRMS (FAB) Calcd. For C₁₅H₁₁NO₄ for C₁₅H₉Cl₂NO₂: C, 58.85;H, 2.97; N, 4.58. Found: C, [M⁺]: 269.0688. Found: 269.0686. 58.62; H,2.78; N, 4.53. 2,5-Dichloro-3-(7-methyl-1H-indol-3-yl)-[1,4]benzoquinone73% 2,5-Dihydroxy-3-(7-methyl-1H-indol-3-yl)- Blue needles frombenzene/hexane. mp 140-141° C.. ¹H [1,4]benzoquinone NMR(d₆-acetone):1.00(3H, t, J=7.2Hz), 1.77(2H, h, J=7.5Hz), Dark green needles fromacetone/hexane. mp 207° C. 2.93(2H, dd, J=9.0, 16.5Hz), 7.03(1H, s),7.06 (dec). ¹H NMR(d₆-acetone): 0.98(3H, t, J=7.6Hz), (1H, t, J=7.2Hz),7.24(1H, dd, J=1.5, 6.9Hz), 7.34(1H, 1.76(2H, h, J=7.6Hz), 2.89(1H, t,J=7.6Hz), s), 7.67(1H, dd, J=1.2, 3.0Hz), 11.09(1H, br s). ¹³C NMR6.02(1H, s), 6.94-7.00(2H, m), 7.39-7.39(1H, m), (d₆-acetone): 13.9,23.6, 33.4, 107.2, 119.5, 120.5, 122.1, 7.54(1H, d, J=2.8Hz),8.4-10.0(2H, br s), 10.58 125.9, 126.3, 130.1, 133.4, 135.4, 136.5,139.2, 143.7, 1H, br s). ¹³C NMR(d₆-acetone): 13.7, 23.3, 33.3, 177.6,177.9. IR(KBr): 3401, 3062, 2958, 2929, 2871, 103.2, 105.1, 112.2,119.4, 119.7, 121.4, 125.4, 2858, 1670, 1572, 1434, 1115, 1023cm⁻¹.Anal. Calcd. for 126.9, 127.2, 134.3. IR(KBr): 3421, 3330, 2955,C₁₇H₁₃Cl₂NO₂: C, 61.10; H, 3.92. Found: C, 60.94; H, 4.13. 2868, 1615,1534, 1354, 1297, 1230, 1195cm⁻¹. HRMS (EI): calcd. for C₁₇H₁₅NO₄297.1001, found 297.1001. 3-(7-tert-butyl-1H-indol-3-yl)-2,5-dichloro-83% 3-(7-tert-butyl-1H-indol-3-yl)-2,5-dihydroxy- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 189-190° C.. ¹HDark green needles from acetone/hexane. mp 210-211° C.. NMR(d₆-acetone):1.54(9H, s), 7.06(1H, t, J=7.8Hz), ¹H NMR(d₆-acetone): 1.53(9H, s), 6.037.15(1H, d, J=6.6Hz), 7.27(1H, d, J=7.8Hz), 7.37(1H, (1H, s), 6.98(1H,t, J=8.0Hz), 7.08(1H, dd, J=1.2, s), 7.64(1H, d, J=3.3Hz), 10.77(1H, brs). ¹³C NMR(d₆- 7.6Hz), 7.36(1H, d, J=8.0Hz), 7.51(1H, d, J=2.8Hz),acetone): 34.5, 106.8, 118.9, 119.3, 120.3, 127.0, 129.5, 9.0-10.0(2H,br s), 10.35(1H, br s). ¹³C 133.4, 133.6, 134.4, 137.0, 139.3, 143.7,177.6, 177.9. IR NMR(d₆-acetone): 29.8, 34.2, 103.2, 104.6, 112.0,(KBr): 3438, 3064, 2963, 1659, 1565, 1422, 1269, 1113, 118.1, 119.3,120.1, 126.8, 128.0, 133.5, 133.6. IR 1026, 750cm⁻¹. Anal. Calcd. forC₁₈H₁₅Cl₂NO₂: C, 62.08; (KBr): 3337, 2967, 2866, 1631, 1360, 1299, 1223,H, 4.34. Found: C, 62.32; H, 4.58. 931cm⁻¹. HRMS (EI): calcd. forC₁₈H₁₇NO₄ 311.1158, found 311.1158.2,5-Dichloro-3-(7-phenyl-1H-indol-3-yl)-[1,4]benzoquinone 76%2,5-Dihydroxy-3-(7-phenyl-1H-indol-3-yl)- Blue needles frombenzene/hexane. mp 185-186° C.. ¹H [1,4]benzoquinone NMR(d₆-acetone):7.21-7.25(2H, m), 7.35(1H, s), 7.38-7.44 Dark green needles fromacetone/hexane. mp 210-211° C.. (2H, m), 7.47-7.53(2H, m), 7.66(2H, dd,J=1.2, 8.4Hz), ¹H NMR(d₆-acetone): 6.04(1H, s), 7.1-7.2 7.70(1H, d,J=2.8Hz), 10.94(1H, br s). ¹³C NMR (2H, m), 7.40(1H, t, J=7.4Hz),7.4-7.7(7H, m), (d₆-acetone): 118.0, 119.0, 120.5, 120.9, 121.1, 122.5,9.0-10.2(2H, br s), 10.58(1H, br s). ¹³C NMR(d₆- 126.7, 127.7, 128.7,129.2, 130.9, 132.6, 133.5, 133.9, 138.9, acetone): 103.3, 105.1, 119.9,121.3, 121.4, 121.7, 139.1, 143.8, 143.8, 177.6, 178.0. IR(KBr): 3424,3328, 125.9, 127.4, 127.9, 128.1, 128.6, 129.1, 133.8, 3137, 3069, 3029,1675, 1651, 1568, 1426, 755cm⁻¹. Anal. 139.4. IR(KBr): 3402, 3325, 3029,2950, 2923, Calcd. for C₂₀H₁₁Cl₂NO₂: C, 65.24; H, 3.01; N, 3.80. Found:1633, 1524, 1428, 1343, 760cm⁻¹. HRMS (EI): C, 65.44; H, 3.44; N, 3.60.calcd. for C₂₀H₁₃NO₄ 331.0845, found 331.0844.2,5-Dichloro-3-(7-methoxy-1H-indol-3-yl)- 75%2,5-Dihydroxy-3-(7-methoxy-1H-indol-3-yl)- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 183-184° C.. ¹HDark green needles from acetone/hexane. mp 202-203° C.. NMR(CDCl₃):3.94(3H, s), 6.67(1H, d, J=7.6Hz), 6.96 ¹H NMR(d₆-acetone): 3.91(3H, s),5.98 (1H, dd, J=0.8, 8.0Hz), 7.09(1H, t, J=8.0Hz), 7.17(1H, (1H, s),6.64(1H, d, J=5.7Hz), 6.91(1H, t, J=6.0Hz), s), 7.50(1H, d, J=3.2Hz),8.94(1H, br s). ¹³C NMR(d₆- 7.09(1H, d, J=6.0Hz), 7.51(1H, d, J=1.8Hz),acetone): 55.1, 102.5, 107.2, 114.4, 120.9, 126.7, 127.4, 7.8-10.2(2H,br s), 10.63(1H, br s). ¹³C NMR 129.8, 133.4, 136.7, 139.2, 143.8,146.9, 177.6, 178.0. IR (d₆-acetone): 55.0, 101.7, 103.2, 105.2, 112.1,114.8, (KBr): 3391, 3152, 1667, 1626, 1499, 1419, 1114, 1013. 119.7,126.7, 127.1, 128.4, 146.6. IR(KBr): 3390, Anal. Calcd. for C₁₅H₉Cl₂NO₃:C, 55.93; H, 2.82; N, 4.35. 3311, 2928, 1634, 1501, 1449, 1354, 1097,933cm^(−1.) Found: C, 56.16; H, 2.94; N, 4.23. HRMS (EI): calcd. forC₁₅H₁₁NO₅ 285.0637, found 285.0636.3-(7-Benzyloxy-1H-indol-3-yl)-2,5-dichloro- 84%3-(7-Benzyloxy-1H-indol-3-yl)-2,5-dihydroxy- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 174-175° C.. ¹HDark green needles from acetone/hexane. mp 202° C. NMR(d₆-acetone):5.29(2H, s), 6.85(1H, dd, J=1.6, 6.8Hz), (dec). ¹H NMR(d₆-DMSO):5.23(2H, s), 5.84(1H, 6.99-7.07(2H, m), 7.35(1H, t, J=7.2Hz), 7.36(1H,s), 6.38(1H, d, J=7.6Hz), 6.81(1H, d, J=8.0Hz), s), 7.42(2H, dt, J=1.2,7.2Hz), 7.57(1H, d, J=7.2Hz), 6.87(1H, d, J=8.0Hz), 7.26-7.32(2H, m),7.36 7.66(1H, d, J=2.8Hz), 11.25(1H, br s). ¹³C NMR(d₆- (2H, t,J=7.2Hz), 7.52(2H, d, J=7.6Hz), 9.0-10.0 acetone): 70.0, 103.8, 107.2,114.6, 120.8, 127.0, 127.6, (2H, br s), 11.42(1H, br s). ¹³CNMR(d₆-DMSO): 127.97, 128.0, 128.6, 129.7, 129.8, 133.4, 137.6, 139.2,69.8, 103.5, 104.4, 105.5, 112.7, 115.0, 119.6, 126.7, 143.8, 146.0,177.6, 178.0. IR(KBr): 3380, 3066, 2918, 127.5, 128.2, 128.4, 128.8,129.1, 138.0, 145.6. IR 2872, 1674, 1657, 1567, 1428, 1244, 1111cm⁻¹.Anal. KBr): 3421, 2960, 2925, 2856, 1631, 1501cm⁻¹. Calcd. forC₂₁H₁₃Cl₂NO₃: C, 63.34; H, 3.29. Found: C, HRMS (EI): calcd. forC₂₁H₁₅NO₅ 361.0950, found 63.50; H, 3.38. 361.0950.3-(7-Fluoro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 75%3-(7-Fluoro-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 177-178° C.. ¹H [1,4]benzoquinone NMR(d₆-acetone):6.98(1H, dd, J=8.0, 11.2Hz), 7.09 Dark blue needles from acetone/hexane.mp 201° C. (1H, dt, J=4.8, 8.0Hz), 7.24(1H, d, J=8.0Hz), 7.40(1H, (dec).IR(KBr): 3420, 3277, 3162, 2923, 2861, 1632, s), 7.76(1H, d, J=2.8Hz),11.41(1H, br s). ¹³C NMR(d₆- 1357, 1299, 1234cm⁻¹. ¹H NMR(d₆-acetone):6.03 acetone): 106.8, 107.0, 117.6, 120.5, 120.6, 130.6, 130.8, (1H, s),6.90(1H, dd, J=8.0, 11.6Hz), 6.99(1H, dt, 131.1, 132.6, 133.4, 138.8,143.9, 177.5, 177.9. IR(KBr): J=4.8, 8.0Hz), 7.34(1H, d, J=8.0Hz),7.65(1H, J=2.8Hz), 3395, 3096, 1671, 1573, 1503, 1423, 1265, 1236, 1109,9.0-10.2(2H, br s), 11.00(1H, br s). ¹³C 1038cm⁻¹. Anal. Calcd. forC₁₄H₆Cl₂FNO₂: C, 54.22; H, NMR(d₆-acetone): 103.3, 106.0, 106.2, 111.3,118.0, 1.95. Found: C, 54.36; H, 2.09. 119.3, 119.4, 128.1, 128.3,130.7. HRMS (EI): calcd. for C₁₄H₈FNO₄ 273.0437, found 273.0440.3-(7-Chloro-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 70%3-(7-Chloro-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 213-214° C.. ¹H [1,4]benzoquinone Dark blue needlesfrom NMR(d₆-acetone): 7.14(1H, t, J=8.0Hz), 7.27(1H, dd, J=0.8,acetone/hexane. mp 207° C.(dec). ¹H NMR(d₆- 7.6Hz), 7.40(1H, s),7.41(1H, dd, J=0.8, 8.0Hz), acetone): 6.04(1H, s), 7.04(1H, t,J=10.4Hz), 7.20 7.77(1H, d, J=3.2Hz), 11.23(1H, br s). ¹³C NMR(d₆- (1H,d, J=10.0Hz), 7.66(1H, d, J=4.0Hz), 9.0-10.2 acetone): 108.2, 120.8,121.4, 122.0, 128.0, 130.9, 131.0, (2H, br s), 10.86(1H, br s). ¹³CNMR(d₆- 133.7, 138.9, 144.1, 177.6, 178.1. IR(KBr): 3406, 3071,acetone): 103.4, 106.1, 111.2, 116.4, 120.1, 120.9, 2950, 1678, 1649,1542, 1508, 1434, 1247, 1204cm⁻¹. Anal. 121.0, 128.4, 128.7, 133.3.IR(KBr): 3428, 3310, Calcd. for C₁₄H₆Cl₃NO₂: C, 51.49; H, 1.85; N, 4.29.Found: 3091, 1626, 1354, 1296, 1063, 930cm⁻¹. HRMS C, 51.59; H, 2.01; N,4.28. (EI): calcd. for C₁₄H₈ClNO₄ 289.0142, found 289.0138.3-(7-Bromo-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 71%3-(7-Bromo-1H-indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 191-192° C.. ¹H [1,4]benzoquinone NMR(d₆-acetone):7.09(1H, t, J=8.0Hz), 7.41(1H, s), Dark blue needles fromacetone/hexane. mp 225-226° C.. 7.44(2H, dt, J=0.8, 8.0Hz), 7.77(1H, d,J=1.6Hz), ¹H NMR(d₆-acetone): 6.04(1H, s), 6.99(1H, t, J=7.8Hz),11.14(1H, br s). ¹³C NMR(d₆-acetone): 104.8, 108.0, 7.35(1H, dd, J=0.6,7.8Hz), 7.54(1H, d, 121.0, 121.6, 124.9, 127.5, 130.6, 130.7, 133.4,138.1, J=8.1Hz), 7.66(1H, d, J=2.7Hz), 8.4-10.0(2H, 138.7, 143.9, 177.4,178.0. IR(KBr): 3368, 3160, 3060, br s), 10.76(1H, br s). ¹³CNMR(d₆-acetone): 103.4, 2972, 2866, 1662, 1561, 1262, 1098, 1012,882cm⁻¹. Anal. 104.3, 106.2, 111.3, 120.6, 121.4, 124.1, 128.4, Calcd.for C₁₄H₆BrCl₂NO₂: C, 45.32; H, 1.63; N, 3.78. 130.8, 134.7. IR(KBr):3330, 2959, 2929, 2854, Found: C, 45.47; H, 1.75; N, 3.81. 1617, 1531,1433, 1354, 1292, 932cm⁻¹. HRMS (EI): calcd. for C₁₄H₈BrNO₄ 332.9637,found 332.9637.3-(7-Benzyl-1H-indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 85%3-(7-Benzyl-1H-indol-3-yl)-2,5-dichloro- Blue needles frombenzene/hexane. mp 159-160° C.. ¹H [1,4]benzoquinone NMR(d₆-acetone):4.30(2H, s), 7.01(1H, d, J=6.6Hz), Dark green needles fromacetone/hexane. mp 206-207° C.. 7.08(1H, t, J=7.2Hz), 7.14-7.22(1H, m),7.24-7.33(4H, ¹H NMR(d₆-acetone): 4.28(2H, s), 6.02 m), 7.35(1H, s),7.66(1H, d, J=3.0Hz), 10.95(1H, s). ¹³C (1H, s), 6.92-7.03(2H, m),7.14-7.34(5H, m), 7.41 NMR(d₆-acetone): 37.0, 107.3, 117.8, 120.0,120.6, 122.5, (1H, d, J=7.5Hz), 7.54(1H, d, J=2.7Hz), 8.6-10.3 122.9,125.0, 126.3, 128.6, 129.0, 130.2, 132.5, 133.4, (2H, br s), 10.49(1H,br s). ¹³C NMR(300Hz, d₆- 135.3, 140.3, 143.7, 177.5, 177.9. IR(KBr):3414, 3059, acetone): 37.1, 103.2, 105.2, 112.0, 119.6, 120.2, 1676,1656, 1566, 1434, 1266, 1237, 1113, 1033cm⁻¹. Anal. 122.2, 124.1, 126.1,127.1, 127.4, 128.5, 128.9, Calcd. for C₂₁H₁₃Cl₂NO₂: C, 65.99; H, 3.43;N, 3.66. Found: 135.2, 140.7. IR(KBr): 3422, 3326, 3084, 3027, C, 65.74;H, 3.49; N, 3.71. 1612, 1532, 1438, 1353cm⁻¹. HRMS (EI): calcd. forC₂₁H₁₅NO₄ 345.1001, found 345.1001.2,5-Dichloro-3-[7-(2-methyl-benzyl)-1H-indol-3-yl]- 96%2,5-Dihydroxy-3-[7-(2-methyl-benzyl)-1H-indol-3- [1,4]benzoquinoneyl]-[1,4]benzoquinone Blue needles from benzene/hexane. mp 101-102° C..¹H Dark green needles from acetone/hexane. mp 220° C. NMR(d₆-acetone):2.27(3H, s), 4.28(2H, s), 6.75(1H, d, J=6.9Hz), (dec). ¹HNMR(d₆-acetone): 2.27(3H, s), 4.25(2H, 7.00-7.23(5, m), 7.30(1H, d,J=8.1Hz), 7.33) s), 6.02(1H, s), 6.70(1H, d, J=7.2Hz), 6.92-7.04 (1H,s), 7.68(1H, d, J=3.3Hz), 11.00(1H, br s). ¹³C NMR (2H, m),7.05-7.15(2H, m), 7.18(1H, t, J=7.2Hz), (d₆-acetone): 19.1, 34.5, 107.3,119.9, 120.1, 120.6, 122.0, 7.56(1H, d, J=2.4Hz), 8.8-10.2(2H, br s),10.56 122.4, 124.1, 126.0, 126.2, 126.4, 129.4, 130.3, 133.4, (1H, brs). ¹³C NMR(d₆-acetone): 19.1, 34.6, 103.2, 135.5, 136.8, 138.0, 139.2,143.7, 177.6, 177.9. IR(KBr): 105.2, 112.1, 119.5, 120.2, 121.6, 123.2,126.1, 3414, 3060, 2920, 2857, 1656, 1561, 1433, 1237, 1110, 126.5,126.9, 127.4, 129.4, 130.2, 135.4, 136.8, 1031cm⁻¹. Anal. Calcd. forC₂₂H₁₅Cl₂NO₁₂: C, 66.68; H, 138.3. IR(KBr): 3304, 2966, 1699, 1624,1434, 3.82; N, 3.53. Found: C, 65.88; H, 3.85; N, 3.79. 1350, 1218cm⁻¹.HRMS (EI): calcd. for C₂₂H₁₇NO₄ 359.1158, found 359.1157.3-(1H-Benzo[g]indol-3-yl)-2,5-dichloro-[1,4]benzoquinone 70%3-(1H-Benzo[g]indol-3-yl)-2,5-dihydroxy- Blue needles frombenzene/hexane. mp 210-211° C.. ¹H [1,4]benzoquinone NMR(d₆-acetone):7.18-7.25(1H, m), 7.38-7.62(6H, m), Dark green needles fromacetone/hexane. mp 210° C. 7.72-7.75(1H, m), 7.97(1H, d, J=8.1Hz),8.49(1H, d, J=8.1Hz), (dec). ¹H NMR(d₆-acetone): 6.05(1H, s), 7.42(1H,11.85(1H, br s). ¹³C NMR(d₆-acetone): 111.0, dt, J=1.5, 6.9Hz),7.45-7.56(2H, m), 7.60-7.68 118.0, 119.8, 120.4, 120.9, 121.3, 124.0,124.4, 125.9, (2H, m), 7.93(1H, d, J=8.1Hz), 8.36(1H, d, J=8.1Hz),127.8, 128.7, 133.4. IR(KBr): 3340, 3063, 2922, 1675, 8.8-10.5(2H, brs), 11.51(1H, br s). ¹³C 1651, 1558, 1272, 1224, 1021, 871cm⁻¹. HRMS(FAB) : NMR(d₆-acetone): 103.2, 106.4, 111.9, 119.8, 120.3, calculatedfor C₁₈H₉Cl₂NO₂ 341.0010. Found 341.0013. 122.1, 122.4, 123.9, 125.4,128.6, 130.5, 130.8. IR (KBr): 3318, 3158, 3060, 2923, 2855, 1612, 1353,1291, 929, 814cm⁻¹. HRMS (FAB) : calcd. for C₁₈H₁₁NO₄ 305.0688, found305.0686. 3-(2,6-Dimethyl-1H-indol-3-yl)-2,5-dichloro- 73%3-(2,6-Dimethyl-1H-indol-3-yl)-2,5-dihydroxy- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 114-115° C.. ¹HDark green needles from acetone/hexane. mp 210° C. NMR(d₆-acetone):2.34(3H, s), 2.39(3H, s), 6.86(1H, d, J=8.7Hz), (dec). ¹HNMR(d₆-acetone): 2.28(3H, s), 2.37(3H, 7.12(1H, d, J=8.1Hz), 7.17(1H,s), 7.37(1H, s), 6.03(1H, s), 6.78(1H, d, J=8.7Hz), 7.07-7.14 s),10.46(1H, br s). ¹³C NMR(d₆-acetone): 13.0, 21.1, (2H, m), 8.4-9.9(2H,br s), 10.09(1H, br s). ¹³C 102.6, 111.0, 119.6, 121.5, 125.4, 130.9,133.4, 136.4, NMR(d₆-acetone): 12.8, 21.2, 103.4, 110.5, 119.6, 136.8,140.1, 144.0, 176.9, 178.1. IR(KBr): 3266, 3064, 120.7, 126.5, 129.9,134.8, 136.4. IR(KBr): 3384, 2958, 2921, 1677, 1654, 1568, 1466, 1258,1033cm⁻¹. Anal. 3324, 2975, 2912, 2857, 1637, 1352, 1295, 1228, Calcd.for C₁₆H₁₁Cl₂NO₂: C, 60.02; H, 3.46; N, 4.37. Found: 1184cm⁻¹. HRMS(EI): calcd. for C₁₆H₁₃NO₄ C, 59.76; H, 3.54; N, 4.32. 283.0845, found283.0849. 3-(2,7-Dimethyl-1H-indol-3-yl)-2,5-dichloro- 84%3-(2,7-Dimethyl-1H-indol-3-yl)-2,5-dihydroxy- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 95-96° C.. ¹H NMRDark green needles from acetone/hexane. mp 206° C. (d₆-acetone):2.35(3H, s), 2.49(3H, s), 6.86-6.96(2H, m), (dec). ¹H NMR(d₆-acetone):2.32(3H, s), 2.47(3H, 7.07(1H, d, J=6.9Hz), 7.36(1H, s), 10.51(1H, brs). ¹³C s), 6.05(1H, s), 6.85(1H, s), 6.88(1H, d, J=7.2Hz),NMR(d₆-acetone): 13.1, 16.4, 105.4, 117.6, 120.1, 120.4, 7.07(1H, dd,J=2.1, 7.2Hz), 8.5-10.0(2H, br 122.2, 127.2, 133.4, 135.4, 137.2, 139.8,140.1, 144.0, s), 10.16(1H, br s). ¹³C NMR(d₆-acetone): 12.8, 176.9,178.1. IR(KBr): 3362, 3064, 2919, 2860, 1675, 16.4, 102.6, 103.4, 112.0,117.6, 119.2, 119.7, 121.3, 1620, 1453, 1269, 1243, 884cm⁻¹. Anal.Calcd. for 128.2, 135.2, 135.4. IR(KBr): 3331, 2945, 2856, C₁₆H₁₁Cl₂NO₂:C, 60.02; H, 3.46; N, 4.37. Found: C, 60.19; 1629, 1559, 1454, 1185,932cm⁻¹. HRMS (EI): H, 3.59; N, 4.31. calcd. for C₁₆H₁₃NO₄ 283.0845,found 283.0846. 3-(6,7-Dimethyl-1H-indol-3-yl)-2,5-dichloro- 75%3-(6,7-Dimethyl-1H-indol-3-yl)-2,5-dihydroxy- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane. mp 184-185° C.. IRDark green needles from acetone/hexane. mp 220° C. (KBr): 3387, 3071,2920, 2860, 1675, 1551, 1506, 1433, (dec). ¹H NMR(d₆-acetone): 2.35(3H,s), 2.43(3H, 1263cm⁻¹. ¹H NMR(d₆-acetone)2.36(3H, s), 2.46(3H, s), s),6.01(1H, s), 6.86(1H, d, J=8.1Hz), 7.25(1H, d, 6.95(1H, d, J=8.4Hz),7.12(1H, d, J=8.0Hz), 7.33(1H, J=7.8Hz), 7.50(1H, d, J=2.7Hz),8.8-10.2(2H, s), 7.61(1H, d, J=2.8Hz), 10.84(1H, s). ¹³C NMR(d₆- br s),10.38(1H, br s). ¹³C NMR(d₆-acetone): 12.7, acetone): 12.6, 18.6, 107.2,118.9, 119.2, 123.1, 124.0, 18.8, 103.1, 118.2, 112.5, 119.1, 122.2,123.1, 125.0, 129.6, 130.0, 133.4, 136.6, 139.1, 143.6, 177.7, 178.0.Anal. 126.9, 128.6, 129.9. IR(KBr): 3340, 3150, 2921, Calcd. forC₁₆H₁₁Cl₂NO₂. C, 60.02; H, 3.46; N, 4.37. Found: 2869, 1615, 1533,1351cm⁻¹. HRMS (EI): calcd. for C, 59.98; H, 3.59; N, 4.23 C₁₆H₁₃NO₄283.0845, found 283.0850.3-(5,6-Methylenedioxy-1H-indol-3-yl)-2,5-dichloro- 57%3-(5,6-Methylenedioxy-1H-indol-3-yl)-2,5- [1,4]benzoquinonedihydroxy-[1,4]benzoquinone Blue needles from benzene/hexane. mp 170°C.(dec). ¹H Dark green needles from acetone/hexane. mp 335° C.NMR(d₆-acetone): 5.95(2H, s), 6.82(1H, s), 6.99(1H, s), (dec). ¹HNMR(d₆-acetone): 5.91(2H, s), 6.00(1H, 7.34(1H, s), 7.54(1H, d,J=3.0Hz), 10.82(1H, br s). ¹³C s), 6.92(1H, d, J=0.8Hz), 6.94(1H, d,J=0.4Hz), NMR(d₆-acetone): 92.6, 100.3, 101.0, 107.1, 120.2, 128.9,7.44(1H, d, J=2.8Hz), 8.8-10.2(2H, br s), 10.42 131.3, 133.3, 136.4,139.2, 143.6, 143.7, 145.3, 177.6, (1H, br s). ¹³C NMR(d₆-acetone):92.4, 100.6, 178.0. IR(KBr): 3337, 3066, 2971, 2874, 1668, 1566, 1426,100.64, 100.8, 103.0, 109.8, 126.2, 126.3, 131.2, 1042, 942cm⁻¹. Anal.Calcd. for C₁₅H₇Cl₂NO₄: C, 53.60; H, 142.8, 144.7. IR(KBr): 3420, 3077,2937, 2844, 2.10. Found: C, 53.61; H, 2.23. 1624, 1470, 1330cm⁻¹. HRMS(EI): calcd. for C₁₅H₉NO₆ 299.0430, found 299.0428.3-(5,6-Dimethoxy-1H-indol-3-yl)-2,5-dichloro- 65%3-(5,6-Dimethoxy-1H-indol-3-yl)-2,5-dihydroxy- [1,4]benzoquinone[1,4]benzoquinone Blue needles from benzene/hexane mp 186-187° C.. IRDark green needles from acetone/hexane. mp 335° C. (KBr): 3300, 3040,2952, 2957, 2829, 1634, 1546, 1484, (dec). ¹H NMR(d₆-acetone): 5.91(2H,s), 6.00(1H, 1228, 1087cm⁻¹. ¹H NMR(d₆-acetone): 3.78(3H, s), 3.84 s),6.92(1H, d, J=0.8Hz), 6.94(1H, d, J=0.4Hz), (3H, s), 6.93(1H, s),7.10(1H, s), 7.36(1H, s), 7.56(1H, d, 7.44(1H, d, J=2.8Hz), 8.8-10.2(2H,br s), 10.42 J=2.7Hz), 10.82(1H, br s). ¹³C NMR(d₆-acetone): 55.7, (1H,br s). ¹³C NMR(d₆-acetone): 92.4, 100.6, 56.0, 95.8, 104.7, 106.8,117.6, 119.0, 120.6, 129.1, 130.8, 100.64, 100.8, 103.0, 109.8, 126.2,126.3, 131.2, 133.4, 143.6, 145.9, 147.9, 177.7, 177.9. Anal. Calcd. for142.8, 144.7. IR(KBr): 3420, 3077, 2937, 2844, C₁₆H₁₁Cl₂NO₄: C, 54.57;H, 3.15. Found: C, 51.03; H, 3.32. 1624, 1470, 1330cm⁻¹. HRMS (EI):calcd. for C₁₅H₉NO₆ 299.0430, found 299.0428.

EXAMPLE 7 Inhibition of Phosphatase Cdc25B

[0120] Using procedures known to those skilled in the art, the compoundslisted in Table 3 were screened against Cdc25A, Cdc25B,and Cdc25C at 50μM. Similar amounts of inhibition were seen for all three isoforms ofCdc25. To analyze these effects further, the compounds were thenscreened against Cdc25B in a 3 pt. IC-50, using 1, 7 and 50 μM. Severalof the compounds were also screened with an 8 pt. IC-50 process, using0.1-10 μM, allowing determination of Hill slopes. Further data (notshown) demonstrates that these compounds are competitive vs. substrate,indicating that they bind at the active site of Cdc25. Overall, theseresults show that these are preferred compound for treating aCdc25-related cell proliferative disorder. TABLE 3 Percent Inhibition atplate IC50 IC50 50 uM compound CHEMISTRY No. Ser. No. (3 pt) (8 pt)Cdc25 A Cdc25 B Cdc25 C 2,5-dihydroxy-3(1H-indol-3-yl)-[1,4]- 2AZL-I-197 14.2 16.5 55 75 69 benzoquinone2,5-dihydroxy-3-(1-methyl-1H-indol-3-yl)-[1,4]- 2B ZL-I-194 184.5 63 4219 benzoquinone 2,5-dihydroxy-3-(2-methyl-1H-indol-3-yl)-[1,4]- 2CZL-I-186 138.3 35 9 5 benzoquinone2,5-dihydroxy-3-(2-ethyl-1H-indol-3-yl)-[1,4]- 2D ZL-I-174 33.4 51 36 14benzoquinone 2,5-dihydroxy-3-(2-cyclopropyl-1H-indol-3-yl)- 2E ZL-I-1842.3 24.4 79 32 0 [1,4]-benzoquinone2,5-dihydroxy-3-(2-isopropyl-1H-indol-3-yl)-[1,4]- 2F ZL-I-185 8.3 58 130 benzoquinone 2,5-dihydroxy-3-[2-(1-methylcycloproyl)-1H- 2G LD-I-2053.6 49 17 0 indol-3-yl]-[1,4]-benzoquinone2,5-dihydroxy-3-(2-tert-butyl-1H-indol-3-yl)-[1,4]- 2H ZL-I-187 13.9 3111 0 benzoquinone 2,5-dihydroxy-3-[2-(1-methylcyclohexyl)-1H- 3A LD24B82.9 69 11 22 indol-3-yl]-[1,4]-benzoquinone2,5-dihydroxy-3-(2-phenyl-1H-indol-3-yl)-[1,4]- 3B ZL-I-207 22.2 93 3818 benzoquinone 2,5-dihydroxy-3-[2-(1,1-dimethyl-allyl)-1H-indol- 3CZL-I-202 40.3 40 0 21 3-yl]-[1,4]-benzoquinone2,5-dihydroxy-3-(4-fluoro-1H-indol-3-yl)-[1,4]- 3D LD-I-217 1.2 15.9 595 0 benzoquinone 2,5-dihydroxy-3-(4-chloro-1H-indol-3-yl)-[1,4]- 3E LD9B3.0 8.4 67 21 0 benzoquinone2,5-dihydroxy-3-(4-bromo-1H-indol-3-yl)-[1,4]- 3F LD11B 3.1 >2 0 6 54benzoquinone 2,5-dihydroxy-3-(4-methoxy-1H-indol-3-yl)-[1,4]- 3G LD19B7.2 77 21 19 benzoquinone 2,5-dihydroxy-3-(4-benzyloxy-1H-indol-3-yl)-3H LD-I-90 4.6 87 0 2 [1,4]-benzoquinone2,5-dihydroxy-3-(4-methyl-1H-indol-3-yl)-[1,4]- 4A LD13B 6.0 51 9 28benzoquinone 2,5-dihydroxy-3-(5-fluoro-1H-indol-3-yl)-[1,4]- 4B LD-I-20411.7 64 32 23 benzoquinone2,5-dihydroxy-3-(5-chloro-1H-indol-3-yl)-[1,4]- 4C LD3B 2.3 95 32 45benzoquinone 2,5-dihydroxy-3-(5-bromo-1H-indol-3-yl)-[1,4]- 4D LD6B 2.496 55 26 benzoquinone 2,5-dihydoxy-3-(7-methyl-1H-indol-3-yl)- 4EZL-III-198 69.3 10 0 0 [1,4]naphthoquinone2,5-dihydroxy-3-(5-methoxy-1H-indol-3-yl)-[1,4]- 4F LD2B 6.0 15 0 0benzoquinone 2,5-dihydroxy-3-(5-benzyloxy-1H-indol-3-yl)- 4G LD4B 1.8 9650 26 [1,4]-benzoquinone 2,5-dihydroxy-3-(5-methyl-1H-indol-3-yl)-[1,4]-4H LD20B 2.5 94 61 55 benzoquinone2,5-dihydroxy-3-(6-fluoro-1H-indol-3-yl)-[1,4]- 5A LD-I-210 2.0 6.8 9148 90 benzoquinone 2,5-dihydroxy-3-(6-chloro-1H-indol-3-yl)-[1,4]- 5BLD1B 2.4 99 92 81 benzoquinone2,5-dihydroxy-3-(6-benzyloxy-1H-indol-3-yl)- 5C LD-I-214 1.7 89 97 92[1,4]-benzoquinone 2,5-dihydroxy-3-(6-methyl-1H-indol-3-yl)-[1,4]- 5DLD10B 32.3 80 16 28 benzoquinone2,5-dimethoxy-3-(7-fluoro-1H-indol-3-yl)-[1,4]- 5E LD-I-206 125.1 29 6768 benzoquinone 2,5-dihydroxy-3-(7-chloro-1H-indol-3-yl)-[1,4]- 5FLD-I-207 38.0 92 23 54 benzoquinone2,5-dihydroxy-3-(7-bromo-1H-indol-3-yl)-[1,4]- 5G LD-I-216 2.1 93 45 88benzoquinone 2,5-dihydroxy-3-(7-methyl-1H-indol-3-yl)-[1,4]- 5H ZL-I-1754.2 60 0 1 benzoquinone 2,5-dihydroxy-3-(7-propyl-1H-indol-3-yl)-[1,4]-6A LD-I-215 14.1 93 23 79 benzoquinone2,5-dihydroxy-3-(7-prenyl-1H-indol-3-yl)-[1,4]- 6B ZL-I-196 2.1 100 9984 benzoquinone 2,5-dihydroxy-3-(7-geranyl-1H-indol-3-yl)-[1,4]- 6CLD25B 0.1 0.5 99 95 96 benzoquinone2,5-dihydroxy-3-(7-farnecyl-1H-indol-3-yl)-[1,4]- 6D LD26B 0.1 0.5 86 8985 benzoquinone 2,5-dihydroxy-3-(7-benzyl-1H-indol-3-yl)-[1,4]- 6ELD-I-219 1.7 98 97 98 benzoquinone2,5-dihydroxy-3-[7-(2-methyl-benzyl)-1H-indol-3- 6F LD-I-218 0.6 1.1 9097 94 yl]-[1,4]-benzoquinone2,5-dihydroxy-3-(7-tert-butyl-1H-indol-3-yl)-[1,4]- 6G LD22B 2.1 96 3337 benzoquinone 2,5-dihydroxy-3-(7-phenyl-1H-indol-3-yl)-[1,4]- 6HLD-I-143 1.4 98 92 91 benzoquinone2,5-dihydroxy-3-(7-methoxy-1H-indol-3-yl)-[1,4]- 7A LD8B 79.5 36 15 13benzoquinone 2,5-dihydroxy-3-(7-benzyloxy-1H-indol-3-yl)- 7B LD17B 1.698 97 85 [1,4]-benzoquinone2,5-dihydroxy-3-(2,5-dimethyl-1H-indol-3-yl)- 7C ZL-I-199 16.5 61 20 25[1,4]-benzoquinone 2,5-dihydroxy-3-(2-methyl-5-methoxy-1H-indol- 7DZL-I-192 125.9 0 0 31 3-yl)-[1,4]-benzoquinone2,5-dihydroxy-3-(2-methyl-5-chloro-1H-indol-3- 7E ZL-I-193 52.2 91 60 81yl)-[1,4]-benzoquinone 2,5-dihydroxy-3-(2,6-dimethyl-1H-indol-3-yl)- 7FLD-I-209 206.7 46 16 0 [1,4]-benzoquinone2,5-dihydroxy-3-(2,7-dimethyl-1H-indol-3-yl)- 7G LD15B 38.5 20 0 0[1,4]-benzoquinone 2,5-dihydroxy-3-(5,6-methylenedioxy-1H-indol- 7HLD-I-125 3.7 96 88 63 3-yl)-[1,4]-benzoquinone2,5-dihydroxy-3-(5,6-dimethoxy-1H-indol-3-yl)- 8A LD16B 116.9 39 19 20[1,4]-benzoquinone 2,5-dihydroxy-3-(6,7-dimethyl-1H-indol-3-yl)- 8BLD-I-208 12.8 90 32 20 [1,4]-benzoquinone2,5-dihydroxy-3-(1H-benzo[g]indol-3-yl)-[1,4]- 8C LD-I-213 2.8 98 79 75benzoquinone 2-(2-tert-butyl-1H-indol-3-yl)-5-(7-tert-butyl-1H- 8DZL-III-273-I 5.8 indol-3-yl)-3-chloro-6-hydroxy-[1,4]- benzoquinoneDAQ-B1 8E ZL-II-241 0.9 2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-8F ZL-III-268 11.2 (1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(1- 8G ZL-III-269 12.0methyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(2- 8H ZL-II-193 5.8methyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(2- 9A ZL-III-262 5.6cyclopropyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(2- 9B ZL-III-261 5.0isopropyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(2- 9C ZL-III-263 5.1tert-butyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(2- 9D ZL-III-260 6.1phenyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(4- 9E ZL-III-278 13.7methoxy-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(4- 9F ZL-III-277 2.3benzyloxy-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(5- 9G ZL-III-275 8.7fluoro-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(5- 9H ZL-III-270 80.3methoxyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(5- 10A ZL-III-271 0.6benzyloxy-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(5- 10B ZL-III-272 7.2methyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(6- 10C ZL-III-276 5.3fluoro-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(6- 10D ZL-III-279 5.3methyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(7- 10E ZL-III-267 4.8methyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(7- 10F ZL-III-273 0.9tert-butyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5- 10G ZL-III-264 14.6(2,5-dimethyl-1H-indol-3-yl)-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(2- 10H ZL-III-266 11.5methyl-5-methoxy-1H-indol-3-yl)-[1,4]- benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-3,6-dihydroxy-5-(2- 11A ZL-III-265 8.4methyl-5-chloro-1H-indol-3-yl)-[1,4]- benzoquinone2,5-dihydroxy-3-(1-methyl-1H-indol-3-yl)-6- 11B ZL-III-185 7.9phenyl-[1,4]-benzoquinone2,5-dihydroxy-3,6-bis(2-methyl-1H-indol-3-yl)l- 11C ZL-III-274 15.7[1,4]-benzoquinone 2,5-dihydoxy-3-(2-methyl-1H-indol-3-yl)- 11DZL-III-168-II 18.0 [1,4]naphthoquinone2,5-bis(2-tert-butyl-1H-indol-3-yl)-3-chloro-6- 11E ZL-III-263-I 22.9hydroxy-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-5-(1H-indol-3-yl)-3- 11F ZL-III-268-I49.9 chloro-6-hydroxy-[1,4]-benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-5-(7-methyl-1H- 11G ZL-III-267-I 33.8indol-3-yl)-3-chloro-6-hydroxy-[1,4]- benzoquinone2-(2-tert-butyl-1H-indol-3-yl)-5-(2-phenyl-1H- 11H ZL-III-260-I 6.7indol-3-yl)-3-chloro-6-hydroxy-[1,4]- benzoquinone

EXAMPLE 8 Inhibition of Phosphatase H1

[0121] Using procedures known to those skilled in the art, the compoundslisted in Table 3 were screened against recombinant vaccinia H1phosphatase using FMOP as a fluorogenic substrate. Compounds wereinitially screened at 1 micromolar concentration. Several compounds inthis series completely abolish enzymatic activity at this concentration,while the majority of compounds have low enzyme inhibition activity.

[0122] The foregoing is illustrative of the present invention, and isnot to be construed as limiting thereof. The invention is defined by thefollowing claims, with equivalents of the claims to be included therein.

What is claimed is:
 1. An acid-catalyzed method of producing a compoundof formula I:

wherein: R₁ and R₃ are each independently hydrogen, OH, SH, halo, amino,alkoxy, aminoalkyl, alkyl, aryl, acyloxy, or (acyloxy)alkyl; R₂ ishydrogen, aryl, heteroaryl, indolyl, alkyl, alkoxy, phenoxy, anilino,amino, halo, acyloxy, or (acyloxy)alkyl; or R₁ and R₂ together form anaromatic ring; R₅ is hydrogen, C₁-C₇ alkyl, C₂-C₇ alkenyl, C₂-C₇alkynyl, arylalkyl, or aryl; R₄ is hydrogen, branched or unbranchedsaturated C₁-C_(n) alkyl, branched or unbranched unsaturated C₁-C_(n)alkyl, alkylcarboxy, C₂-C_(m) alkenyl, alkynyl, alkenylcarboxy, aryl,alkylaryl hydroxy, hydroxyalkyl, C₁-C_(n) alkoxy, nitro, halo,trihalomethyl, amido, carboxamido, carboxy, sulfonyl, sulfonamido,amino, mercapto, or 2-methylbut-2-en-4-yl, wherein n is an integer from2-12, preferably 2-7, and m is an integer from 3-12, preferably 3-7; andR₆ and R₇ are each independently hydrogen, cycloalkyl, alkyl, alkoxy,halo, aryl, heteroaryl, phenoxy, anilino, amino, or form part of anaromatic ring wherein said aromatic ring may be substituted; [Is thisenough?] which method comprises: reacting a substituted or unsubstituted2,5-dichloro-1,4-benzoquinone compound of formula II:

 wherein R₁, R₂ and R₃ are as defined above; with at least one pyrroleof the formula III:

 wherein R₄—R₇ are as defined above; in a polar organic solvent and inthe presence of an acid to produce a first intermediate; and thenreacting the first intermediate with an oxidization agent to producesaid compound of formula I.
 2. The method of claim 1, wherein R1 and R2together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—.
 3. Themethod of claim 1, wherein n is 2-7 and m is 3-7.
 4. The method of claim1, further comprising: reacting said compound of formula I with analkali metal hydroxide to produce a compound of the formula:

wherein R₂ and R₄—R₇ are as defined above.
 5. The method of claim 1,wherein the organic solvent is an aprotic solvent selected from thegroup consisting of tetrahydrofuran (THF), acetonitrile, and mixturesthereof.
 6. The method of claim 1, wherein the acid is HCl.
 7. Themethod of claim 1, wherein the acid is H₂SO₄.
 8. The method of claim 1,wherein the acid is AcOH.
 9. The method of claim 1, wherein theoxidization agent is dichlorodicyanobenzoquinone.
 10. The method ofclaim 1, wherein the oxidization agent is Ag₂CO₃.
 11. The method ofclaim 1, wherein the reaction is conducted at a temperature from about−10° C. to about 100° C.
 12. An acid-catalyzed method of producing acompound of formula V:

wherein: R₁ and R₃ are each independently OH, SH, halo, amino, alkoxy,aminoalkyl, hydrogen, alkyl, aryl, acyloxy, or (acyloxy)alkyl; R₂ ishydrogen, aryl, heteroaryl, indolyl, alkyl, alkoxy, phenoxy, anilino,amino, halo, acyloxy, or (acyloxy) alkyl; R₁ and R₂ can constitute partof an aromatic ring; R₅ is hydrogen, C₁-C₇ alkyl, C₂-C₇ alkenyl, C₂-C₇alkynyl, arylalkyl, or aryl; and R₄ and R₆—R₉ are each independentlyhydrogen, branched or unbranched C₁-C_(n) alkyl, alkylcarboxy, C₂-C_(m)alkenyl, alkynyl, alkenylcarboxy, aryl, alkylaryl, hydroxy,hydroxyalkyl, C₁-C_(n) alkoxy, nitro, halo, trihalomethyl, amido,carboxamido, carboxy, sulfonyl, sulfonamido, amino, mercapto, or2-methylbut-2-en-4-yl, wherein n is an integer from 2-12, and m is aninteger from 3-12; which method comprises: reacting a substituted orunsubstituted 2,5-dichloro-1,4-benzoquinone compound of the formula:

 wherein R₁, R₂ and R₃ are as defined above; with at least one indole ofthe formula:

 wherein R₄—R₉ are as defined above; in a polar organic solvent and inthe presence of an acid to produce a first intermediate; and thenreacting the first intermediate with an oxidization agent to producesaid compound of formula V.
 13. The method of claim 12, wherein R1 andR2 together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—. 14.The method of claim 12, wherein n is 2-7 and m is 3-7.
 15. The method ofclaim 12, further comprising: reacting said compound of formula I withan alkali metal hydroxide to produce a compound of the formula:

wherein R₂ and R₄—R₉ are as defined above.
 16. The method of claim 12,wherein the organic solvent is an aprotic solvent selected from thegroup consisting of tetrahydrofuran (THF), acetonitrile, and mixturesthereof.
 17. The method of claim 12, wherein the acid is HCl.
 18. Themethod of claim 12, wherein the acid is H₂SO₄.
 19. The method of claim12, wherein the acid is AcOH.
 20. The method of claim 12, wherein theoxidization agent is dichlorodicyanobenzoquinone.
 21. The method ofclaim 12, wherein the oxidization agent is Ag₂CO₃.
 22. The method ofclaim 12, wherein the reaction is conducted at a temperature from about−10° C. to about 100° C.
 23. A compound of the formula I:

wherein: R₁ and R₃ are each independently hydrogen, OH, SH, halo, amino,alkoxy, aminoalkyl, alkyl, aryl, acyloxy, or (acyloxy)alkyl; R₂ ishydrogen, aryl, heteroaryl, indolyl, alkyl, alkoxy, phenoxy, anilino,amino, or halo; or R₁ and R₂ together form an aromatic ring; R₅ ishydrogen, C₁-C₇ alkyl, C₂-C₇ alkenyl, C₂-C₇ alkynyl, arylalkyl, or aryl;R₄ is hydrogen, branched or unbranched saturated C₁-C_(n) alkyl,branched or unbranched unsaturated C₁-C_(n) alkyl, alkylcarboxy,C₂-C_(m) alkenyl, alkynyl, alkenylcarboxy, aryl, alkylaryl hydroxy,hydroxyalkyl, C₁-C_(n) alkoxy, nitro, halo, trihalomethyl, amido,carboxamido, carboxy, sulfonyl, sulfonamido, amino, mercapto, or2-methylbut-2-en-4-yl, wherein n is an integer from 2-12, and m is aninteger from 3-12; and R₆ and R₇ are each independently hydrogen,cycloalkyl, alkyl, alkoxy, halo, aryl, heteroaryl, phenoxy, anilino,amino, or form part of an aromatic ring wherein said aromatic ring issubstituted or unsubstituted.
 24. The compound of claim 23, wherein R1and R2 together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—.25. The method of claim 23, wherein n is 2-7 and m is 3-7.
 26. Apharmaceutical composition comprising a compound of claim 23 in apharmaceutically acceptable carrier.
 27. A compound of the formula V:

wherein: R₁ and R₃ are each independently OH, SH, halo, amino, alkoxy,aminoalkyl, hydrogen, alkyl, aryl, acyloxy, or (acyloxy)alkyl; R₂ ishydrogen, aryl, heteroaryl, indolyl, alkyl, alkoxy, phenoxy, anilino,amino, halo, acyloxy, or (acyloxy)alkyl; R₁ and R₂ can constitute partof an aromatic ring; R₅ is hydrogen, C₁-C₇ alkyl, C₂-C₇ alkenyl, C₂-C₇alkynyl, arylalkyl, or aryl; and R₄ and R₆—R₉ are each independentlyhydrogen, branched or unbranched C₁-C_(n) alkyl, alkylcarboxy, C₂-C_(m)alkenyl, alkynyl, alkenylcarboxy, aryl, alkylaryl, hydroxy,hydroxyalkyl, C₁-C_(n) alkoxy, nitro, halo, trihalomethyl, amido,carboxamido, carboxy, sulfonyl, sulfonamido, amino, mercapto, or2-methylbut-2-en-4-yl, wherein n is an integer from 2-12, and m is aninteger from 3-12.
 28. The compound of claim 27, wherein R1 and R2together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—.
 29. Thecompound of claim 27, wherein n is 2-7 and m is 3-7.
 30. Apharmaceutical composition comprising a compound of claim 27 in apharmaceutically acceptable carrier.
 31. A method of treating aproliferative disease in a subject in need thereof, comprisingadministering to said subject, in an amount effective to treat saidproliferative disease, a compound of Formula I as given in claim 23 or acompound of Formula V as given in claim 27 in an amount effective totreat said proliferative disease.
 32. The method of claim 31, wherein R1and R2 together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—.33. The method of claim 31, wherein n is 2-7 and m is 3-7.
 34. A methodaccording to claim 31, wherein said proliferative disease is selectedfrom the group consisting of ovarian cancer, breast cancer, coloncancer, gastric carcinomas, non-small cell lung cancer, andnon-Hodgkin's lymphoma.
 35. A method for treating a viral infection in asubject so afflicted, said method comprising administering to thesubject a compound of the Formula I as given in claim
 23. 36. The methodof claim 35, wherein R1 and R2 together form —CH═CH—CH—, —CH═CH—CH═CH—,or —CH═CH—CH═CH—CH═CH—.
 37. The method of claim 35, wherein n is 2-7 andm is 3-7.
 38. The method according to claim 35, wherein said subject isa mammal.
 39. The method according to claim 38, wherein said mammal is ahuman.
 40. The method according to claim 35, wherein said viralinfection is of the family Poxviridae.
 41. The method according to claim35, wherein said viral infection is of the family Filoviridae.
 42. Themethod according to claim 35, wherein said viral infection is of thefamily Herpesviridae.
 43. The method according to claim 35, wherein saidviral infection is of the family Hepadnaviridae.
 44. The methodaccording to claim 35, wherein said viral infection is of the familyRetroviridae.
 45. The method according to claim 35, wherein saidadministration is oral.
 46. The method according to claim 35, whereinsaid administration is by injection.
 47. A method for treating a viralinfection in a subject so afflicted; said method comprisingadministering to the subject a compound of the Formula V as given inclaim
 27. 48. The method of claim 47, wherein R₁ and R₂ together form—CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—.
 49. The method ofclaim 47, wherein n is 2-7 and m is 3-7.
 50. The method according toclaim 47, wherein said subject is a mammal.
 51. The method according toclaim 50, wherein said mammal is a human.
 52. The method according toclaim 47, wherein said viral infection is of the family Poxviridae. 53.The method according to claim 47, wherein said viral infection is of thefamily Filoviridae.
 54. The method according to claim 47, wherein saidviral infection is of the family Herpesviridae.
 55. The method accordingto claim 47, wherein said viral infection is of the familyHepadnaviridae.
 56. The method according to claim 47, wherein said viralinfection is of the family Retroviridae.
 57. The method according toclaim 47, wherein said administration is oral.
 58. The method accordingto claim 47, wherein said administration is by injection.
 59. A methodfor treating a neurodegenerative disease in a subject so afflicted, saidmethod comprising administering to the subject a compound of Formula Ias given in claim 23 in an amount effective to treat saidneurodegenerative disease.
 60. The method of claim 59, wherein R1 and R2together form —CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—.
 61. Themethod of claim 59, wherein n is 2-7 and m is 3-7.
 62. The methodaccording to claim 59, wherein said neurodegenerative disease isAlzheimer's disease.
 63. The method according to claim 59, wherein saidneurodegenerative disease is Parkinson's disease.
 64. The methodaccording to claim 59, wherein said neurodegenerative disease ismultiple sclerosis.
 65. The method according to claim 59, wherein saidneurodegenerative disease is amyotropic lateral sclerosis.
 66. Themethod according to claim 59, wherein said administration is by oraladministration.
 67. The method according to claim 59, wherein saidadministration is by injection.
 68. A method for treating aneurodegenerative disease in a subject so afflicted, said methodcomprising administering to the subject a compound of Formula V as givenin claim 27 in an amount effective to treat said neurodegenerativedisease.
 69. The method of claim 68, wherein R1 and R2 together form—CH═CH—CH—, —CH═CH—CH═CH—, or —CH═CH—CH═CH—CH═CH—.
 70. The method ofclaim 68, wherein n is 2-7 and m is 3-7.
 71. The method according toclaim 68, wherein said neurodegenerative disease is Alzheimer's disease.72. The method according to claim 68, wherein said neurodegenerativedisease is Parkinson's disease.
 73. The method according to claim 68,wherein said neurodegenerative disease is multiple sclerosis.
 74. Themethod according to claim 68, wherein said neurodegenerative disease isamyotropic lateral sclerosis.
 75. The method according to claim 68,wherein said administration is oral.
 76. The method according to claim68, wherein said administration is by injection.